generality and definition

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=22 BGCOLOR="#FFFFFF" TEXT="#080000" bgproperties="fixed" background="041000d2egerdp.gif"> <div> </div> </td> </tr><tr> <td valign="top" width=145 BGCOLOR="#333399" TEXT="#080000" background="040a2c00erkjzj.gif"> <div>   <SCRIPT>  </SCRIPT>  <form method="POST" action="http://mindit.netmind.com/mindit.shtml" target="_top"> <input type="hidden" name="SOURCE" value="510"> <table border="0" cellpadding="5" cellspacing="0"><tr><td align="center"> <font face="arial,helvetica" size="-1"><b>Click to receive email <br>when this page is updated</b></font></td> </tr><tr><td align="center"> <input type="hidden" name="DOC_TITLE" value="danilhammoudi_site"> <input type="image" src="http://mindit.netmind.com/images/mindit510.gif" border="0"></td> </tr><tr><td align="center"> <font face="arial,helvetica" size="-2">•<b> Powered by <a href="http://www.netmind.com" target="_top">NetMind</a> </b>•</font> </td></tr></table></form>   </div> <div>  <img src="HTMLobj-99/aniGif.gif" border="0" align="bottom" width="100" height="120">  </div> <div>  <img src="HTMLobj-100/aniGif.gif" border="0" align="bottom" width="100" height="157">  </div> <div> CREATED:</div> <div> 6/25/98</div> <div> LAST UPDATE 9/12/2000</div> </td> <td valign="top" height=458 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> <FONT SIZE="5" COLOR="#336600" FACE="Times New Roman" ><I>TUMORS</I></FONT><FONT SIZE="1" COLOR="#663399" FACE="Times New Roman" >    </FONT> |    <B> </B><FONT SIZE="2" COLOR="#0000BF" FACE="Times New Roman" ><A HREF="index.htm" TARGET="_top" TITLE="TUMORS"><U><B>home</B></U></A></FONT></div> <div> <B>generality and definition</B><B>   |   </B><A HREF="id63.htm" TARGET="_top" TITLE="chart"><U>chart</U></A><B>   |   </B><A HREF="id22.htm" TARGET="_top" TITLE="diag and treatment"><U>diag and treatment</U></A><B>   |   </B><A HREF="id18.htm" TARGET="_top" TITLE="specificity"><U>specificity</U></A><B>   |   </B><A HREF="id19.htm" TARGET="_top" TITLE="pictures"><U>pictures</U></A><B>   |   </B><A HREF="id23.htm" TARGET="_top" TITLE="cancer by organ"><U>cancer by organ</U></A><B>   |   </B><A HREF="id24.htm" TARGET="_top" TITLE="My Photos"><U>My Photos</U></A><B>   |   </B><A HREF="id20.htm" TARGET="_top" TITLE="Related Links"><U>Related Links</U></A><B>   |   </B><A HREF="id21.htm" TARGET="_top" TITLE="Contact Me"><U>Contact Me</U></A></div> <div> <IMG SRC="04207040.gif" border=0 width="263" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>generality and definition</B></div> <div> TUMORS ARE THE MOST SCARRY DISEASE THAT ALL OF US FAIR , WHY BECAUSE IT KILL, ALTHOUGH WITH OUR NEW MEDICINE AND PREVENTION WE CAN DETECT AND TREAT THE TUMORS IN A SUFFICIENT WAY.</div> <div> WHEN WE SAY TUMOR THE GENERAL PUBLIC THINK CANCER, </div> <div> THERE IS TWO TYPE OF TUMORS THE BENIGN AND THE MALIGNANT.</div> <div> THE MALIGNANT WHICH WE CALL CANCER IS THE WORST SINCE IT KILL.</div> <div> WE ALL HAVE A MALIGNANT TUMOR IN OUR BODY, WITH THE DIFFERENCE THAT AS A WEAKNESS MAY BE AND PREDISPOSITION SOME WILL DECLARE IT AND GET AND SOME DON'T.</div> <div> IN THIS CHAPTER I WILL TRY TO DEVELOP AS MICH AS I CAN AND MY KNOWLEGE ABOUT THE TUMOR, THE TYPE, CLINIC PATHOLOGY AND TREATMENT.</div> <bR> <bR> <div> THE TUMORS TOUCH ANY ORGAN SOME MORE THE OTHER, NO DIFFERENTIAL OF AGE BUT THE EVOLUTION OF IT SEEMS THE MALIGNANT TYPE GROW SLOWER IN THE ELDERLY THAN IN THE YOUNG.</div> <bR> <div> SOME TYPE OF CANCER ARE SEEN IN KIDS AND NOT IN ADULT.</div> <div> AND SOME CANCER ARE MORE FREQUENT IN MALE THAN FEMALE AND VIS VERSA</div> <div> OTHER NAME = NEOPLASIA</div> <bR> <div>  <FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B>Definition of Neoplasia</B></FONT></div> <div> "An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change."</div> <bR> <div> OTHER DEFINITION MORE SIMPLE TO MEMORIZED</div> <div> NEOPLASIA : The presence of abnormal cells forming a growth or tumor, unable to perform their normal functions, and replacing healthy cells</div> <bR> <div> <IMG SRC="06968f00.gif" border=0 width="360" height="240" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">DR.ED FREIDLANDER [HE IS GOOD IN THIS TYPE OF PICTURES]</div> <div> <B><U>Terms Related to Neoplasia</U></B></div> <bR> <div> <B>Neoplasia:</B><B> new growth = tumour </B></div> <div> <B>Malignant:</B><B> a tumour capable of metastasis</B></div> <div> <B>Metastasis:</B><B> spread of a tumour from the site of primary growth to a distant site</B></div> <div> <B>Cancer:</B><B> a malignant neoplasm or tumour (? from the Latin "crab")</B></div> <div> <B>Oncology:</B><B> the study of neoplasms</B></div> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most neoplasms arise from the clonal expansion of a single cell that has undergone neoplastic transformation. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The transformation of a normal to a neoplastic cell can be caused by a chemical, physical, or biological agent (or event) that directly and irreversibly alters the cell genome.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neoplastic cells are characterized by the loss of some specialized functions and the acquisition of new biological properties, foremost, the property of relatively autonomous (uncontrolled) growth.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neo</B><B>pl</B><B>astic cells pass on their heritable biological characteristics to progeny cells. </B></div> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A malignant neoplasm manifests a greater degree of autonomy, is capable of invasion and metastatic spread, may be resistant to treatment, and may cause death. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A benign neoplasm has a lesser degree of autonomy, is usually not invasive, does not metastasize, and generally produces no great harm if treated adequately</B></div> <bR> <div> Anaplasia is a characteristic property of cancer cells and denotes a lack of normal structural and functional characteristics (undifferentiation). </div> <bR> <bR> <div> <B><U>Nomenclature and Classification [SEE</U></B><A HREF="http://PATHOLOGYLECTURES.HOMESTEAD.COM" TARGET="_top" TITLE="http://PATHOLOGYLECTURES.HOMESTEAD.COM"><U><B><U> CELL INJURY AND ADAPTATION</U></B></U></A><B><U>]</U></B></div> <bR> <bR> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypertrophy:</U></B></I><I> </I>increase in the size of normal cells</div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hyperplasia:</U></B></I> increase in the number of cells ,</div> <div> Hyperplasia is an absolute increase in the number of cells per unit of tissue, is generally initiated and regulated by definable, such as hormonal, stimuli, and may be useful to the host (physiologic and adaptive hyperplasia)</div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Metaplasia:</U></B></I> a normal cell type for that site changes to another normal cell type that should not normally be present at that site e.g. bronchial epithelium changing to squamous epithelium in response to bronchial "irritation".. Metaplasia denotes a change of one type of adult cell to another, is usually an adaptive response to an inflammatory or other abnormal stimulus, and is often reversible.</div> <bR> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dysplasia:</U></B></I> loss in the uniformity of the individual cells as well as a loss in their architectural orientation. </div> <div> Tissue will return to normal upon removal of dysplastic stimulus.</div> <div> Dysplasia is an abnormal atypical cellular proliferation (atypical hyperplasia), is usually reversible, and is not a tumor but possibly a precursor in some circumstances. </div> <bR> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neoplasia:</U></B></I><I><B><U> </U></B></I>differs from dysplasia by being irreversible on removal of the stimulus.</div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Differentiation versus anaplasia:</U></B></I> refers to the extent to which parenchymal cells resemble comparable normal cells, both morphologically and functionally.</div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Parenchyma:</U></B></I> neoplastic cells</div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Supportive Stroma:</U></B></I><I> </I>non-neoplastic connective tissue & blood vessels</div> <bR> <div> The suffix "-oma" means tumor and usually denotes a benign neoplasm, as in fibroma, lipoma, and so forth, but sometimes implies a malignant neoplasm, as with so-called melanoma, hepatoma, and seminoma, or even a nonneoplastic lesion, such as a hematoma, granuloma, or hamartoma. </div> <bR> <div> The suffix "-blastoma" denotes a neoplasm of embryonic cells, such as neuroblastoma of the adrenal or retinoblastoma of the eye. </div> <bR> <bR> <div> Histogenesis is the origin of a tissue and is a method of classifying neoplasms on the basis of the tissue cell of origin. Adenomas are benign neoplasms of glandular epithelium. Carcinomas are malignant tumors of epithelium. Sarcomas are malignant tumors of mesenchymal tissues. </div> <bR> <bR> <div> Oncology (G. onkos, tumor,+ logia) is the study or science of neoplasms, including the etiology and pathogenesis. </div> <div> Some nonneoplastic cellular proliferations , such as hyperplasia, metaplasia, and dysplasia must be distinguished from neoplasms. </div> <div> .</div> <div>  malignant tumors differ from benign tumors in four biological properties: structure, rate of growth, invasive growth, and disseminated growth by metastasis. Of these characteristics, metastasis is a unique feature of malignant neoplasms, is a major factor in the fatal course of the disease, and is the main deterrant to its successful treatment. Given that fact, whenever possible , it is of paramount clinical importance to diagnose and treat potentially malignant tumors before the progression to metastasis. </div> <bR> <bR> <div> <B><U>Grading and staging of cancer</U></B></div> <bR> <div> The grade and stage of a cancer has a significant impact on the management and prognosis of the patient. The stage is usually the more important parameter.</div> <bR> <bR> <div> <I><B><U>(1) Grading</U></B></I><I> </I></div> <div>  a tumour involves estimating its <I>degree of differentiation</I> and the <I>number of mitoses</I> - Grade I well differentiated to Grade IV undifferentiated. Undifferentiated malignancies usually are more aggressive and carry a poorer prognosis. Criteria have been established for different tumour types to assist in grading e.g. mucin secretion by an adenocarcinoma of the colon suggests differentiation.</div> <bR> <bR> <div> <B><U>(2) Staging</U></B><B><U> of a tumour</U></B> TNM</div> <div> is based on the <I>size of the primary and extent of spread of the tumour</I>, both to the regional nodes and to more widespread sites (blood borne). The TNM system is the more commonly used staging system:</div> <div> T = size of the primary tumour; T0 in situ, then T1-T4 depending on size;</div> <div> N = nodal involvement; N0 no nodes involved, then N1-N3 depending on the extent of nodal involvement; </div> <div> M = distant metastases other than by lymphatics; M0 no distant metastases, M1-M2 depending on extent of metastasis.</div> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U><IMG SRC="1ffb08c0.gif" border=0 width="432" height="396" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></FONT><FONT SIZE="5" COLOR="#000000" FACE="Arial" >Staging of Malignant Neoplasms </FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Stage Definition </FONT><B>Tis</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >In situ, non-invasive (confined to epithelium) </FONT><B>T1</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Small, minimally invasive within primary organ site </FONT><B>T2</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Larger, more invasive within the primary organ site </FONT><B>T3</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Larger and/or invasive beyond margins of primary organ site </FONT><B>T4</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Very large and/or very invasive, spread to adjacent organs </FONT><B>N0</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >No lymph node involvement </FONT><B>N1</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Regional lymph node involvement </FONT><B>N2</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Extensive regional lymph node involvement </FONT><B>N3</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >More distant lymph node involvement </FONT><B>M0</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >No distant metastases </FONT><B>M1</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Distant metastases present </FONT></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="513" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FF0000 HEIGHT= 30 ><NOBR><div> <B>Staging of Malignant Neoplasms </B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="138"><div> <B>Stage </B></div> </tD> <tD VALIGN=CENTER WIDTH="360"><div> <B>Definition </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>Tis</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> In situ, non-invasive (confined to epithelium) </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>T1</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> Small, minimally invasive within primary organ site </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>T2</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> Larger, more invasive within the primary organ site </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="138"><div> <B>T3</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="360"><div> Larger and/or invasive beyond margins of primary organ site </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="138"><div> <B>T4</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="360"><div> Very large and/or very invasive, spread to adjacent organs </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>N0</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="360"><div> No lymph node involvement </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>N1</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="360"><div> Regional lymph node involvement </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>N2</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00><NOBR><div> Extensive regional lymph node involvement </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>N3</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00><NOBR><div> More distant lymph node involvement </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>M0</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="360"><div> No distant metastases </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="138"><div> <B>M1</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="360"><div> Distant metastases present </div> </tD> </tR> </TABLE></div> <bR> <div> <FONT SIZE="5" COLOR="#000000" FACE="Arial" >Grading of Malignant Neoplasms </FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Grade Definition </FONT><B>I</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Well differentiated </FONT><B>II</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Moderately differentiated </FONT><B>III</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Poorly differentiated </FONT><B>IV</B> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >Nearly anaplastic </FONT></div> <bR> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="513" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FF0000 HEIGHT= 30 ><NOBR><div> <B>Grading of Malignant Neoplasms </B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="235"><div> <B>Grade </B></div> </tD> <tD VALIGN=CENTER WIDTH="263"><div> <B>Definition </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="235"><div> <B>I</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="263"><div> Well differentiated </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="235"><div> <B>II</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="263"><div> Moderately differentiated </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="235"><div> <B>III</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="263"><div> Poorly differentiated </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="235"><div> <B>IV</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#0000FF WIDTH="263"><div> Nearly anaplastic </div> </tD> </tR> </TABLE></div> <bR> <div> <IMG SRC="200f8d80.gif" border=0 width="504" height="216" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <bR> <div> <B><U>Cell cycling, types of cells and their susceptibility to carcinogens</U></B></div> <div> <I>Labile cells:</I> continuously dividing cells that cycle through mitosis throughout life e.g. surface epithelia, excretory ducts, epithelia of the gastrointestinal and urinary tracts, bone marrow and haemopoietic tissue.</div> <div> <I>Stable cells:</I> low level of replication but can undergo mitosis in response to stimuli. Usually sit in G<FONT SIZE="1" COLOR="#000000" FACE="Arial" >0</FONT>. Examples are parenchymal cells of glandular organs (liver, kidney pancreas), mesenchymal cells (fibroblasts, smooth muscle & endothelial cells, chondrocytes and osteocytes) </div> <div> <I>Permanent cells:</I> cannot undergo mitotic division in postnatal life (neurones, cardiac muscle).</div> <div> Most neoplasms are from labile and, to a lesser extent, stable cells, since dividing cells are more susceptible to carcinogens.</div> <div> Most neoplasms arise in cells/tissues exposed to the external environment e.g skin, respiratory and gastrointestinal mucosae, and the female genital tract.</div> <bR> <bR> <bR> <div> <B><U><IMG SRC="202f43b0.gif" border=0 width="500" height="315" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="203f47b0.gif" border=0 width="500" height="379" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="597" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FF0000 HEIGHT= 30 WIDTH="583"><div> <B>Oncogenesis </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 ><NOBR><div> <B>Mechanism </B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="374"><div> <B>Action </B></div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> <B>Example </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER ROWSPAN=6 HEIGHT= 16 WIDTH="103"><div> <B>Growth Promotion</B> </div> </tD> <tD VALIGN=CENTER WIDTH="374"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="374" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Overexpression of growth factor receptors (such as epidermal growth factor, or EGF) making cells more sensitive to growth stimuli </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> c-erb-B2 </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Increased growth factor signal transduction by an oncogene that lacks the GTPase activity that limits GTP induction of cytoplasmic kinases that drive cell growth </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> ras </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Overexpression of a gene product by stimulation from an oncogene (such as ras) </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> c-sis </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Lack of normal gene regulation through translocation of a gene where it is controlled by surrounding genes to a place where it is no longer inhibited </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> c-abl </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Binding of oncogene product to the nucleus with DNA transcriptional activation to promote entry into the cell cycle </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> c-myc </div> </tD> </tR> <tR> <tD VALIGN=CENTER ROWSPAN=6 HEIGHT= 16 WIDTH="103"><div> <B>Loss of Tumor Suppressor Gene Function</B> </div> </tD> <tD VALIGN=CENTER WIDTH="374"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="374" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Loss of normal growth inhibition </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> BRCA-1 </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Lack of regulation of cell adhesion with loss of growth control through cell interaction </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> APC </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Loss of down-regulation of growth promoting signal transduction </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> NF-1 </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Loss of regulation of cell cycle activation through sequestation of transcriptional factors </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> Rb </div> </tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="374"><div> Loss of regulation of cell cycle activation through lack of inhibition of cell proliferation that allows DNA repair </div> </tD> <tD VALIGN=CENTER WIDTH="100"><div> p53 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FFFF HEIGHT= 66 WIDTH="103"><div> <B>Limitation of Apoptosis</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="374"><div> Overexpression of gene, activated by translocation, prevents apoptosis </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="100"><div> bcl-2 </div> </tD> </tR> </TABLE></div> <bR> <bR> <div> <B><U>(ii) Benign versus Malignant Neoplasms</U></B></div> <div> * by definition, malignant tumours metastasise (see later), benign tumours do not.</div> <div> * benign tumours are usually innocuous and non-life threatening (except e.g. a benign meningioma, which presses on the brain in the indistensible cranium). </div> <div> * malignant tumours are often life threatening.</div> <div> * benign tumours usually have the suffix "-oma".</div> <div> * malignant tumours are usually called a carcinoma (if of epithelial origin) or a sarcoma (if of mesenchymal origin).</div> <div> malignant tumors differ from benign tumors in four biological properties: structure, rate of growth, invasive growth, and disseminated growth by metastasis. Of these characteristics, metastasis is a unique feature of malignant neoplasms, is a major factor in the fatal course of the disease, and is the main deterrant to its successful treatment. Given that fact, whenever possible , it is of paramount clinical importance to diagnose and treat potentially malignant tumors before the progression to metastasis. </div> <bR> <bR> <div> <B>Biological Properties of Benign and Malignant Neoplasms</B><B> </B></div> <bR> <div> <B> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="495" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="157"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="157" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>Benign</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Malignant</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 HEIGHT= 23 WIDTH="487"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="487" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 66 WIDTH="157"><div> <B>Structure</B></div> </tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>Resemblance to normal cells (well differentiated)</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Abnormal; less similarity to normal cells</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="157"><div> <B>Mitoses</B></div> </tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>Few</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Relatively common</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="157"><div> <B>Growth</B></div> </tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>Usually purely expansive</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Invasive</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="157"><div> <B>Growth rate</B></div> </tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>Slow</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Rapid</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 ><NOBR><div> <B>Growth duration</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>May cease growing</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Rarely cease growing</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 ><NOBR><div> <B>Encapsulation</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>Usually</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Rarely</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="157"><div> <B>Metastasis</B></div> </tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>None</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Frequent</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 66 ><NOBR><div> <B>Effect on host</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="169"><div> <B>Slight harm, due to location or complication</B></div> </tD> <tD VALIGN=CENTER WIDTH="159"><div> <B>Significant harm, due to invasion & metastasis</B></div> </tD> </tR> </TABLE></B></div> <bR> <div> <B>Classification of Common Neoplasms</B> </div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="628" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Tissue of Origin</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> <B>Benign</B></div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> <B>Malignant</B></div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 16 WIDTH="618"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="618" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Epithelium</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Stratified squamous</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Papilloma</div> </tD> <tD VALIGN=CENTER><NOBR><div> Squamous cell carcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Epidermoid carcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Basal cell</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Basal cell carcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Glandular</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Adenoma</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Adenocarcinoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="115"><div> Papilloma</div> </tD> <tD VALIGN=CENTER><NOBR><div> Papillary adenocarcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Cystadenoma</div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> Cystadenocarcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Neuroectoderm</div> </tD> <tD VALIGN=CENTER><NOBR><div> Benign nevus</div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> Malignant melanoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Respiratory tract</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Bronchogenic carcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="243"><div> Urinary tract</div> </tD> <tD VALIGN=CENTER><NOBR><div> Transitional cell</div> <div> papilloma</div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> Transitional cell carcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="243"><div> Renal cell</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Renal tubular adenoma</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Renal cell carcinoma (Hypernephroma)</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="243"><div> Liver cell</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Liver cell adenoma</div> </tD> <tD VALIGN=CENTER><NOBR><div> Hepatocellular carcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="243"><div> Placental</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Hydatidiform mole</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Choriocarcinoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Testicular germ cells</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Seminoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Embryonal carcinoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 16 WIDTH="618"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="618" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Mesenchymal tissue</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Connective tissue</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Fibrous tissue</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Fibroma</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Fibrosarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Adipose tissue</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Lipoma</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Liposarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Cartilage</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Chondroma</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Chondrosarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Bone</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Osteoma</div> </tD> <tD VALIGN=CENTER><NOBR><div> Osteogenic sarcoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Endothelium</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Blood vessels</div> </tD> <tD VALIGN=CENTER><NOBR><div> Hemangioma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="195"><div> Hemangiosarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Hemangio-</div> <div> endothelioma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="195"><div> Kaposi's sarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Lymph vessels</div> </tD> <tD VALIGN=CENTER><NOBR><div> Lymphangioma</div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> Lymphangiosarcoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Synovium</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Synovial sarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Mesothelium</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Malignant mesothelioma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Primitive mesenchyme</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Ewing's sarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Blood cells</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Hematopoietic cells</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Myelogenous leukemia</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Monocytic leukemia</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Lymphoid cells</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Lymphocytic leukemia</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Malignant lymphoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Malignant thymoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="243" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Multiple myeloma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER ROWSPAN=2 HEIGHT= 19 WIDTH="243"><div> B lymphocytes</div> <div> T lymphocytes</div> <div> Histiocytes </div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Hodgkin's disease</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="34" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Histiocytosis X</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="34" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Muscle</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Smooth muscle</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Leiomyoma</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Leiomyosarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Striated muscle</div> </tD> <tD VALIGN=CENTER><NOBR><div> Rhabdomyoma</div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> Rhabdomyosarcoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 16 WIDTH="618"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="618" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Nerve tissue</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Neuroglia</div> </tD> <tD VALIGN=CENTER WIDTH="115"><div> Glioma</div> </tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Nerve sheaths</div> </tD> <tD VALIGN=CENTER><NOBR><div> Neurilemmoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="195"><div> Neurofibrosarcoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Nerve cells</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Neuroblastoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 16 WIDTH="618"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="618" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 ><NOBR><div> <B>More than one cell type</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Salivary glands</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> Malignant mixed tumor</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Renal anlage</div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><div> Wilm's tumor</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="243"><div> Totipotential cells</div> </tD> <tD VALIGN=CENTER><NOBR><div> Benign teratoma</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="195"><div> Teratocarcinoma</div> </tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 16 WIDTH="618"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="618" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 ><NOBR><div> <B>Metastatic (secondary) tumors</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 16 WIDTH="618"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="618" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="243"><div> <B>Unclassified tumors</B></div> </tD> <tD VALIGN=CENTER WIDTH="115"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="115" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="195"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="62"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="62" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="673" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="236"><div> <B>Oncogene </B></div> </tD> <tD VALIGN=CENTER WIDTH="422"><div> <B>Associated Neoplasms </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="236"><div> <B>c-erb-B2</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="422"><div> Breast and ovarian carcinomas </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="236"><div> <B>ras</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="422"><div> Many carcinomas and leukemias </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="236"><div> <B>c-sis</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="422"><div> Gliomas </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="236"><div> <B>c-abl</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> Chronic myelogenous leukemia, acute lymphocytic leukemia </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="236"><div> <B>c-myc</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="422"><div> Lymphomas </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FF00 HEIGHT= 23 WIDTH="236"><div> <B>BRCA-1</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="422"><div> Breast and ovarian carcinomas </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FF00 HEIGHT= 23 WIDTH="236"><div> <B>APC</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="422"><div> Colonic adenocarcinomas </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FF00 HEIGHT= 23 WIDTH="236"><div> <B>NF-1</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="422"><div> Neurofibromas and neurofibrosarcomas </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FF00 HEIGHT= 23 WIDTH="236"><div> <B>Rb</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00><NOBR><div> Retinoblastomas, osteosarcomas, small cell lung carcinomas </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FF00 HEIGHT= 23 WIDTH="236"><div> <B>p53</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="422"><div> Many carcinomas </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FFFF HEIGHT= 23 WIDTH="236"><div> <B>bcl-2</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF><NOBR><div> Chronic lymphocytic leukemia, lymphomas </div> </NOBR></tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <div> <B>What Is Cancer?</B></div> <bR> <div> Cancer is a group of more than 100 different diseases. Cancer occurs when cells become abnormal and keep dividing and forming more cells without control or order. </div> <div> All organs of the body are made of cells. Normally, cells divide to produce more cells only when the body needs them. This orderly process helps keeps us healthy. </div> <div> If cells keep dividing when new cells are not needed, a mass of <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><I><U>tissue</U></I></FONT> forms. This mass of extra tissue, called a growth or <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><I><U>tumor</U></I></FONT>, can be <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><I><U>benign</U></I></FONT> or <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><I><U>malignant</U></I></FONT>. </div> <bR> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Benign tumors</B> are not cancer. They can usually be removed and, in most cases, they do not come back. Most important, cells from benign tumors do not spread to other parts of the body. Benign tumors are rarely a threat to life.</div> <bR> <div>  </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Malignant tumors</B> are cancer. Cancer cells can invade and damage nearby tissues and organs. Also, cancer cells can break away from a malignant tumor and enter the bloodstream or the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><I><U>lymphatic system</U></I></FONT>. This is how cancer spreads from the original (primary) tumor to form new tumors in other parts of the body. The spread of cancer is called <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><I><U>metastasis</U></I></FONT>. </div> <bR> <bR> <div> Most cancers are named for the type of cell or the organ in which they begin. When cancer spreads, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if lung cancer spreads to the liver, the cancer cells in the liver are lung cancer cells. The disease is called metastatic lung cancer (it is not liver cancer). </div> <bR> <div> malignant tumors differ from benign tumors in four biological properties: structure, rate of growth, invasive growth, and disseminated growth by metastasis. Of these characteristics, metastasis is a unique feature of malignant neoplasms, is a major factor in the fatal course of the disease, and is the main deterrant to its successful treatment. Given that fact, whenever possible , it is of paramount clinical importance to diagnose and treat potentially malignant tumors before the progression to metastasis. </div> <div> T<FONT SIZE="3" COLOR="#000000" FACE="Arial" >he gross appearance of neoplasms is highly variable, consistent with the diversity of their origin, size, and biological behavior. </FONT></div> <div> Neoplasms may be firm, hard (scirrhous), or soft, homogeneous or heterogenous in texture, solid or cystic, pale or dark, and discolored by endogenous pigments, hemorrhage, or necrosis. Slowly growing benign tumors often present as an expansive mass that pushes normal tissues aside, are well circumscribed or encapsulated, and are freely movable in relation to adjacent tissues. By contrast, rapidly growing malignant tumors tend to have an indistinct irregular shape, are not encapsulated, and are fixed to adjacent structures by infiltrative growth or disseminated by metastases. </div> <bR> <div> <B><U>(iii) Methods of Classifying Tumours</U></B></div> <bR> <div> The staging of cancers is an evaluation of the extent of tumor spread which is a major consideration in prognosis and therapy: </div> <div> stage 0: carcinoma in situ; </div> <div> stage 1: early local invasion but no metastases; </div> <div> stage 2: limited local invasion and/or minimal regional lymph node involvement; </div> <div> stage 3: extensive local invasion and/or extensive regional lymph node involvement; </div> <div> stage 4: usually inoperable extension of tumor and/or distant lymph node metastases, or distant metastases regardless of the local extent of the tumor. </div> <bR> <div> <B><U>for each type of cancer a specific classification as duke classification for gi, rappaport and arbor for hodgkin's ect....</U></B></div> <bR> <div> The internationally used TNM system of clinical staging of malignant neoplasms uses three symbols with numerical subscripts to designate the extent of neoplastic disease: the size and extent of the primary tumor(T); the presence and extent of regional lymph node (N) metastases; and the presence and extent of distant metastases (M). The TNM system is being used for the staging of malignant tumors of breast, lung, urinary bladder, and other organs. </div> <bR> <bR> <div> <I>(1) Histogenetic</I></div> <div> Classifies tumours by cell of origin:</div> <bR> <bR> <bR> <div> <TABLE BORDER="2" CELLPADDING="2" CELLSPACING="1" WIDTH="726" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" BGCOLOR=#FFFF00 > <tR> <tD VALIGN=TOP HEIGHT= 55 WIDTH="110"><div> <B>TISSUE</B></div> </tD> <tD VALIGN=TOP WIDTH="152"><div> <B>Columnar / glandular</B></div> <bR> </tD> <tD VALIGN=TOP WIDTH="130"><div> <B>Fibrous</B></div> <bR> </tD> <tD VALIGN=TOP><NOBR><div> <B>Smooth Muscle</B></div> <bR> </NOBR></tD> <tD VALIGN=TOP WIDTH="168"><div> <B>Skeletal Muscle</B></div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 110 WIDTH="110"><div> <B>BENIGN</B></div> </tD> <tD VALIGN=TOP WIDTH="152"><div> <B>Adenoma</B></div> <bR> <bR> <bR> <bR> <bR> </tD> <tD VALIGN=TOP WIDTH="130"><div> <B>FibroMA</B></div> </tD> <tD VALIGN=TOP WIDTH="126"><div> <B>Leiomyoma</B></div> </tD> <tD VALIGN=TOP WIDTH="168"><div> <B>Rhabdomyoma</B></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 20 ><NOBR><div> <B>MALIGNANT</B></div> </NOBR></tD> <tD VALIGN=TOP><NOBR><div> <B>Adenocarcinoma</B></div> </NOBR></tD> <tD VALIGN=TOP><NOBR><div> <B>Fibrosarcoma</B></div> </NOBR></tD> <tD VALIGN=TOP><NOBR><div> <B>LEIMYOSARCOMA</B></div> </NOBR></tD> <tD VALIGN=TOP><NOBR><div> <B>RHABDOMYOSARCOMA</B></div> </NOBR></tD> </tR> </TABLE></div> <bR> <div> Exceptions e.g. melanoma is highly malignant and should really be called a melanocarcinoma; basal cell carcinoma of the skin rarely metastasises, but is malignant because it is locally invasive.</div> <bR> <bR> <div> <I>(2) Names of individuals</I></div> <div> Semi-redundant e.g Hodgkin's disease (malignant tumour of lymph nodes = lymphoma, which has no benign counterpart); Grawitz tumour = renal cell carcinoma (arises from tubule cells of kidney).</div> <bR> <bR> <div> <I>(3) Organs</I></div> <div> Hepatoma = liver cell adenoma (tumour of liver parenchymal cells), malignant version = hepatocellular carcinoma.</div> <bR> <bR> <div> <I>(4) Tumours derived from the 3 germ cell layers</I></div> <div> <I>Teratomas:</I> derived from totipotential cells in gonads or in embryonic rests. A teratoma may be benign or malignant (in which case it is sometimes called a teratocarcinoma). Also includes benign dermoid cysts.</div> <bR> <bR> <div> <I>(5) Not true tumours</I></div> <div> Examples of congenital anomalies:</div> <div> <I>Hamartoma:</I> aberrant differentiation of cells that results in a mass of disorganised but mature specialised cells or tissue indigenous to the particular site. e.g. island of cartilage or blood vessels within the lung. Completely benign.</div> <div> <I>Choristoma:</I> an normal ectopic piece of tissue or an organ that is not normally found at that site e.g. a piece of adrenal gland under the capsule of the kidney or a nodule of pancreatic tissue in the submucosa of the small intestine or stomach.</div> <bR> <bR> <div> <B>Differences Between Benign and Malignant Tumours</B></div> <div> Prognostic importance of diagnosing a tumour as benign or malignant.</div> <div> Morphological diagnosis can usually be made but may be difficult and is always subjective.</div> <div> T<FONT SIZE="3" COLOR="#000000" FACE="Arial" >he gross appearance of neoplasms is highly variable, consistent with the diversity of their origin, size, and biological behavior. </FONT></div> <div> Neoplasms may be firm, hard (scirrhous), or soft, homogeneous or heterogenous in texture, solid or cystic, pale or dark, and discolored by endogenous pigments, hemorrhage, or necrosis. Slowly growing benign tumors often present as an expansive mass that pushes normal tissues aside, are well circumscribed or encapsulated, and are freely movable in relation to adjacent tissues. By contrast, rapidly growing malignant tumors tend to have an indistinct irregular shape, are not encapsulated, and are fixed to adjacent structures by infiltrative growth or disseminated by metastases. </div> <bR> <bR> <div> <B>(i) Basic Differences</B></div> <div> <I>(1) Degree of differentiation</I> (resemblance to normal "parent" tissue)</div> <div> Tumours may be:</div> <div> 1. well differentiated</div> <div> 2. moderately differentiated</div> <div> 3. poorly differentiated or anaplastic (primitive cell types)</div> <div> Note that tumour cells may be undergoing uncontrolled proliferation, but may still be able to differentiate into cell types that closely resemble their normal counterparts.</div> <div> * Benign tumours are usually well differentiated.</div> <div> * Malignant tumours may be well or poorly differentiated.</div> <div> Poorly differentiated tumours are usually very "aggressive" (carry a poorer prognosis due to rapid growth, early metastasis and/or poor response to therapy).</div> <div> <I>(2) Rate of tumour growth</I></div> <div> (a) Most benign tumours grow slowly over a period of years; most malignant tumours tend to grow rapidly over a period of months (from discovery!) but also tend to grow erratically.</div> <div> (b) Rate of growth may depend on <I>tissue type</I>: e.g. sarcomas tend to grow more rapidly than epithelial tumours.</div> <div> (c) Rate of growth generally correlates with <I>degree of differentiation</I>, with undifferentiated tumours tending to grow faster.</div> <div> (d) Rarely both benign and malignant tumours may actually <I>stop growing</I> and reduce in size or disappear completely (the so called "miracle" cure) e.g. very rarely, malignant melanoma may regress and disappear.</div> <div> (e) <I>Hormones</I> may influence the rate of growth of a tumour, e.g. leiomyoma (benign fibroid) of uterus may grow rapidly in pregnancy and disappear after menopause (oestrogen dependant). A tumour may produce tumour angiogenesis factor (TAF) to induce vascularisation of a rapidly growing tumour. However, infarction may occur in the centre of rapidly growing tumours. The host may produce tumour necrosis factor (TNF) which activates macrophages and can cause tumour necrosis and cachexia of the host.</div> <div> <I>(3) Local invasion</I></div> <div> Generally benign tumours grow slowly by expansion and develop a fibrous capsule as a consequence of pressure atrophy and fibrosis of surrounding normal tissue.</div> <div> Fibrous capsule usually allows easy surgical enucleation.</div> <div> Some benign tumours are not well encapsulated e.g. a haemangioma (tangle of blood vessels which may appear to permeate the surrounding tissue). Note that some authorities believe that a haemangioma may in fact be a hamartoma (not a true tumour)!</div> <div> Malignant tumours are locally invasive, infiltrating the surrounding tissues, usually giving rise to irregular margins that are not encapsulated.</div> <div> Surgical removal of a malignant tumour requires a wide margin of "normal" tissue to be resected (say 2-3 cm) to ensure that all malignant cells are removed.</div> <div> Malignant tumours may "erode" into normal tissue blood vessels, increasing the likelihood of metastasis (see below).</div> <div> A tumour derived from epithelial cells (e.g mucosal, epidermal or glandular cells) may not initially break through the basement membrane, presumably because no subclone of neoplastic cells has yet developed the capacity to do so (see later). Such a tumour is referred to as a carcinoma <I>in situ</I> and would usually eventually develop the capacity to break through the basement membrane, invade and metastasise.</div> <div> Some tumours are quite invasive but rarely metastasise e.g. basal cell carcinoma of the skin.</div> <div> Malignant cells appear to possess a strong capacity for amoeboid movement, especially sarcomas, hence they are more rapidly invasive.</div> <div> Certain tissues are more susceptible to invasion e.g. the loose subcutaneous tissue, while other tissues are more resistant e.g. cartilage.</div> <div> <I>(4) Metastasis</I></div> <div> By definition, malignant tumours can metastasise, although their ability to do so varies greatly.</div> <div> Note that a tumour does not have to have metastasised before it is labeled malignant; indeed one aim of microscopic diagnosis of "lumps and bumps" is to diagnose malignant tumours before they have the opportunity to metastasise, allowing complete surgical resection and a "cure".</div> <div> <I>(5) Abnormal or aberrant function</I></div> <div> More likely to occur in malignant tumours e.g. the secretion of abnormal or excessive quantities of hormones.</div> <div> <I>(6) Constitutional effects</I></div> <div> More likely to occur in malignant tumours than in benign for a wide range of reasons, including that benign tumours grow much more slowly.</div> <div> <B>(ii) Macroscopic differences between benign and malignant tumours</B></div> <div> Macroscopic parameters to assess when examining a tumour include:</div> <div> I. Location</div> <div> II. Relationship of the tumour to the organ (including ulceration, polyp formation, mass displacement) </div> <div> III. Size (measure it)</div> <div> IV. Shape of the tumour (round, irregular circumference etc.)</div> <div> V. Margins of the tumour: regular or irregular, e.g. a benign papillary tumour looks like raw cauliflower (a regular ordered pattern), while a malignant papillary tumour looks like overcooked cauliflower (falling apart or fungating).</div> <div> VI. Presence of a capsule</div> <div> VII. Inflammatory response around edges (redness)</div> <div> VIII. Colour & texture of the tumour e.g. benign tumours tend to be greyish or white in colour, while malignant tumours tend to appear yellow, soft, squishy & friable, with areas of necrosis & consequent ulceration & bleeding. Alternatively, tumours that have a high collagen content (either as supporting stroma or as neoplastic parenchymal cells) may be "rock" hard, e.g. a fibroadenocarcinoma may be referred to as "scirrhous" [from the Greek: hard or hard swelling].</div> <div> <I>(1) Mass</I></div> <div> A benign tumour grows by expansion, while a malignant tumour both expands and invades surrounding tissue.</div> <div> Benign tumours (generally) are: (1) well circumscribed and round; (2) have a capsule; (3) their size varies enormously; (4) colour and texture: grey or white and uniform.</div> <div> Malignant tumours (generally) have: (1) finger like projections; (2) irregular margins; (3) are not circumscribed; (4) have variable texture and colour, often due to haemorrhage and necrosis.</div> <div> <I>(2) Ulceration</I></div> <div> May form on mucosal surfaces or skin.</div> <div> Benign neoplastic ulcers: rarely occur; tend to have very sharp edges, are shallow and the floor is usually not indurated.</div> <div> Malignant ulcers: tend to have rolled edges and tend to feel hard; are irregular in shape and may be irregularly indurated.</div> <div> <I>(3) Polyps</I></div> <div> Neoplastic tissue protruding from the skin or from a mucosal surface.</div> <div> Benign polyps: usually pedunculated (have a stalk) and have a uniform texture.</div> <div> Malignant polyps: usually sessile (flat); may ulcerate & bleed; often have an indurated base.</div> <div> <I>(4) Diffuse infiltration</I></div> <div> Malignant tumours may invade and replace important tissue e.g. bone marrow, which results in extramedullary haemopoiesis.</div> <div> <B>(iii) Microscopic differences</B></div> <div> <I>(1) Tumour pattern</I></div> <div> Look at the tumour at low power under the microscope and check for such features as:</div> <div> 1. Polyp formation (hyperplastic [dome shaped], pedunculated [stalk] or sessile [flat]), tubular [branching] or villous [test-tube like] arrangement of fronds in a polyp).</div> <div> 2. Ulceration. </div> <div> 3. Invasion through the basement membrane e.g. squamous cell carcinoma invading into dermis.</div> <div> <I>(2) Organisation of tumour cells</I></div> <div> Tumour cells may be organised into structures that resemble their tissue of origin. For example, glandular tumours often form glandular (acinar) tumour structures. The more regular and ordered these structures, the less likely that they are malignant. Glands that are haphazard in size and organisation suggest malignancy.</div> <div> For example, examine the arrangement of individual cells in a gland:</div> <div> <I>Normal:</I> nuclei at base of cells (polarity), single layer of cells of uniform size arranged around lumen of regular size</div> <div> <I>Benign:</I> nuclei remain basal but usually enlarged, may be higher density of cells, but remain regularly related to each other, may be slight increase in mitotic rate with normal mitoses. </div> <div> <I>Malignant:</I> markedly enlarged central nuclei (loss of polarity and increase in nuclear:cytoplasmic ratio to greater than 50%), cells variable in size and shape (pleomorphic), and haphazardly arranged "don't stand up straight" (loss of polarity), cells may become stratified into two layers. Noticeably increased mitotic rate with abnormal mitoses. Cells may become multinucleate. Of course, the malignant glands may become substantially more anaplastic in more malignant tumours and lose all glandular organisation.</div> <div> Another example of the inappropriatness of tumour cell organisation may be found in squamous cell carcinomas, that may form "keratin pearls", an "onion ring" arrangement of squamous cells forming keratin in the centre. Malignancy is suggested by the inappropriateness of forming keratin well away from the surface of the neoplastic epithelium.</div> <div> <I>(3) Cell function and differentiation</I></div> <div> Benign and well differentiated malignant tumours tend to retain their function, while an anaplastic malignant tumour is more likely to loose all function or express bizarre functions, e.g.:</div> <div> (i) Synthesis of mucin: occurs in well differentiated adenocarcinomas but not in anaplastic.</div> <div> (ii) Synthesis of keratin: may occur in abnormal locations (keratin pearls) or not at all in anaplastic tumours. </div> <div> (iii) Synthesis of melanin: a primary melanoma usually is pigmented but occasionally a metastasis from a primary lesion may lose its pigmentation, suggesting more anaplastic change in that subclone of metastatic cells.</div> <div> (iv) The tumour may produce large amounts of normal or abnormal hormones, e.g.:</div> <div> (a) phaeochromocytoma produces large amounts of normal catecholamines (adrenalin and noradrenaline) due to its large bulk; many tumours may produce abnormal "hormones" </div> <div> (b) tumour secretion of abnormal parathyroid hormone resulting in hypercalcaemia.</div> <div> Note: if the hormone is not normally produced by the tissue of origin of the tumour, it is referred to as a paraneoplastic effect - see later.</div> <div> <I>(4) Rate of growth</I></div> <div> Benign: slow with low mitotic rate, well demarcated (encapsulated) expansion.</div> <div> Malignant: rapid with high mitotic rate & abnormal mitoses; irregular border; not encapsulated.</div> <div> After surgery benign tumours are unlikely to recur, while malignant tumours are.</div> <div> <I>(5) Secondary changes</I></div> <div> Vascularity: benign tumours not very vascular (except a haemangioma!); malignant tumours are very vascular.</div> <div> Necrosis/ulceration: not common in benign tumours; common in malignant.</div> <div> <I>(6) Host responses</I></div> <div> Inflammatory response is common around a malignant tumour (tumour seen as "foreign" by immune system). May correlate with prognosis e.g. the greater the lymphocyte infiltration in a melanoma, the better the prognosis.</div> <div> Malignant tumours may excite a strong fibrous (collagenous) response (referred to as desmoplasia).</div> <div> <I>(7) Cellular level</I></div> <div> (a) Size, shape and polarity of cells: malignant more pleomorphic and lost polarity.</div> <div> (b) Nucleus: slightly larger in benign, but in malignant nuclear to cytoplasmic ratio > 50%, hyperchromatic with bizarre shapes and nucleoli. Multinucleate cells. </div> <div> (c) EM features of poorly differentiated malignant cells:</div> <div> 1. Increased chromatin clumping along nuclear membrane</div> <div> 2. Simplified rough endoplasmic reticulum, allowing cell survival in different locations</div> <div> 3. Increased free ribosomes</div> <div> 4. Pleomorphism of mitochondria</div> <div> 5. Decrease in size and number of organelles</div> <div> 6. Sometimes the presence of intermediate filaments</div> <div> * desmin in smooth muscle cells</div> <div> * gliofilaments in glial tumours</div> <div> <B>Metastasis</B></div> <div> Benign tumours do not metastasise, but malignant tumours usually do eventually metastasise, but may not (e.g. Basal Cell Carcinoma of skin rarely metastasises).</div> <div> The treatment of cancer at present is directed towards removing the tumour itself (surgery, chemotherapy, radiotherapy) rather than treating the cause of the cancer (reversing the genetic changes in the neoplastic cells). Hence, "successful" treatment necessitates the removal of the primary tumour and any secondary deposits (metastases).</div> <div> <B>(i) Factors that increase likelihood of metastasis</B></div> <div> (1) The larger the tumour</div> <div> (2) The older the tumour </div> <div> (3) The less differentiated the tumour</div> <div> (4) Certain cell types more likely to metastasise e.g. sarcomas (when patient presents usually > 50% already have metastases).</div> <div> <B>(ii) How does Cancer spread?</B></div> <div> <I>(1) Seeding: in a body cavity.</I></div> <div> e.g. an ovarian tumour may spread through the peritoneal cavity, a lung tumour may spread through the pleural cavity. Seeding may also occur in the pericardial space, subarachnoid space and in joint cavities. The peritoneal cavity may become filled with gelatinous neoplastic cells from an ovarian tumour, referred to as pseudo-myxoma peritonei.</div> <div> <I>(2) Lymphatics</I></div> <div> Neoplastic cells infiltrate into lymphatic ducts and are carried (by embolism or permeation) to draining (regional) lymph nodes (form a tumour deposit), and subsequently will spread further through the lymphatics. Most common with carcinomas. Regional lymph nodes may become enlarged initially due to the inflammatory response being generated by a tumour (reactive hyperplasia), prior to spread of the tumour cells.</div> <div> e.g. breast cancer of upper outer quadrant of breast will spread to the axillary lymph nodes and eventually form a palpable mass.</div> <div> Often the macroscopically normal draining lymph nodes for a tumour will be surgically removed at the same time as the primary tumour, to reduce the risk of microscopic deposits being left in the nodes and to allow the pathologist to determine a prognosis (if the nodes show no tumour cells then the prognosis is substantially improved).</div> <div> <I>(3) Haematogenous</I></div> <div> Tumour cells infiltrate into blood vessels and spread through the circulation. This mode of spread is typical of sarcomas. Tumour cells may form distant secondary deposits by passing through:</div> <div> (a) the systemic veins and/or pulmonary arteries: usually end up in the capillaries of the lung,</div> <div> (b) the portal veins: (i.e. from cancers of the stomach and bowel) usually end up in the liver, </div> <div> (c) the pulmonary veins and/or systemic arteries: (e.g. cancers of the lung) may end up anywhere in the body.</div> <div> Note that the lumbar veins anastomose with both the portal veins and with the paravertebral veins, which may allow the passage of tumour cells into the vertebral canal, where the resulting tumour may press on the spinal cord and cause paraplegia.</div> <div> Note also that tumour cells may "seed" in and spread along veins, eventually blocking them e.g. a renal cell carcinoma may spread along the renal vein and obstruct the inferior vena cava, causing massive and catastrophic oedema of the lower trunk and legs.</div> <div> <I>(4) Pagetoid</I></div> <div> e.g. Paget's disease of the nipple (may also very rarely occur around the vulva and the anus). There is intra-epidermal spread of tumour cells. An underlying intra-ductal breast carcinoma spreads along the lumen of the duct and infiltrates into the epidermis around the nipple. The skin of the nipple and areola is fissured, ulcerated and oozing, with inflammatory hyperaemia and oedema and/or ulceration.</div> <div> <I>(5) Implantation (iatrogenic)</I></div> <div> Cells may be "transplanted" by the surgeon's knife (or other medical implements) to a second site. This concept in part underlies the argument that a cancer should be resected at the time of surgical biopsy if a frozen section of the tumour shows malignancy e.g. surgical biopsy of a breast lump.</div> <div> <I>(6) Mucosa to mucosa</I></div> <div> e.g. a cancer of the renal pelvis may spread to the ureters and bladder by the tumour cells being "washed" down the ureters and implanting on the mucosa of the lower urinary tract. Very rare.</div> <div> <I>(7) Perineural spread</I></div> <div> Tumour cells may spread along a nerve in the perineural space. This may cause considerable pain in the distribution of the nerve, which may require surgical removal or ablation of the nerve.</div> <div> <B>(iii) Clonal theory of metastasis</B></div> <div> Over a period of time malignant tumours tend to become more aggressive and acquire greater malignant potential - tumour progression. This implies that individual subclones of a malignant tumour progressively evolve; the phenotypic attributes of these subclones include a greater ability to metastasise successfully.</div> <div> For successful metastasis to occur the malignant cells must be able to complete a series of sequential steps. For example, in the case of haematogenous spread, the steps would include:</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(1) Adhesion to the basement membrane at the site of the tumour</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(2) Release of proteolytic enzymes to break down the b.m. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(3) Amoeboid movement to pass through the extracellular matrix.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(4) Intravasation through the wall of the blood vessel, involving a decrease in the adhesion characteristics of the malignant cells.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(5) Attachment to lymphocytes within the circulation to pass to a distant site (tumour cell embolus).</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(6) Re-attachment to the basement membrane of the blood vessel and extravasation.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(7) Metastatic deposition including the ability to seed and grow within the tissue where the malignant cells are deposited. Malignant cells may initially be dormant. The type of tissue the metastatic cell finds itself in may or may not allow it to grow: the </B><I><B>soil theory of metastasis</B></I><B>. Thus prostate cancer has a propensity for bone marrow, and lung cancer for adrenal tissue. On the other hand metastasis is rare in skeletal muscle and less common in the spleen.</B></div> <div> <B>Tumor Cell Invasion </B></div> <div> In the process of tissue invasion by an epithelial cancer, tumor cells must traverse the barriers of the basement membrane and the stromal extracellular matrix. The sequence of events includes: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">detachment of tumor cells from the primary tumor; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">attachment to basement membrane matrix; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">degradation of basement membrane matrix; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">locomotion and infiltration of tumor cells; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">degradation of extracellular matrix; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">degradation of vascular basement membrane matrix. </div> <div> <B>Tumor Cell Embolization</B> </div> <div> Even though malignant tumor cells may invade lymphatic or blood vessels and enter the circulation, only an extremely small number of embolized cells are apparently able to establish metastatic lesions. For example, experimental animal studies indicate that less than 0.01% (< 1 in 10,000) of cancer cells entering the blood stream give rise to metastatic tumors. Tumor cell invasion of blood, or lymphatic, vessels is not sufficient by itself to establish metastatic tumor growth. The survival and growth of metastatic cells is not a random process but depends upon the selection of cancer cells possessing specific properties needed for metastatic growth. </div> <bR> <bR> <div> <B>Tumor Cell Extravasation</B> </div> <bR> <div> This process involves more than the mere lodging of embolized cancer cells in small vessels, such as capillaries or lymphatics. The sequence of mechanisms includes: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">adhesion to endothelial cells; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">endothelial cell retraction; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">migration; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">degradation of matrix; </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">locomotion. </div> <bR> <bR> <div> The cancer cell attaches to the endothelial surface, induces endothelial retraction, migrates through the breach, dissects beneath the endothelium, degrades the vascular basement membrane, and migrates out of the vascular compartment to form a metastatic tumor. </div> <div> Within a primary cancer, there is a marked cellular heterogeneity of metastatic potential. Factors which influence the establishment of tumor metastases include: genetic instability of the tumor cells; enzymatic degradation of basement membrane collagen; ability to withstand rheologic trauma; size of the tumor cell embolus; interaction with cytotoxic T-cells, natural killer cells, and macrophages; entrapment by fibrin or platelets; surface properties (glycoproteins) which may favor the ability of variant tumor cells to reach and colonize specific organs. </div> <bR> <bR> <div> <B>Routes of Metastasis</B> </div> <bR> <div> M<FONT SIZE="3" COLOR="#000000" FACE="Arial" >alignant tumor cells may spread by three major routes: lymphatics, blood vessels, and implantation (seeding) by physical contact between tumor and normal serosal or mucosal surfaces or surgical instrument</FONT></div> <bR> <div> Carcinomas often metastasize initially to regional lymph nodes and later to lungs, liver, bones, brain, and other organs. Breast carcinomas commonly metastasize first to the adjacent axillary lymph nodes. Bronchogenic carcinomas frequently spread initially to perihilar or mediastinal lymph nodes. Colorectal carcinomas often metastasize first to mesenteric lymph nodes. Carcinomas and sarcomas also often metastasize by hematogeneous routes to lungs, liver, bones, brain, and other sites. Cancer cells reaching venous tributaries of the inferior vena cava flow to the right side of the heart and reach the lungs. Malignant tumor cells entering the portal venous circulation flow to the liver. Cancer cells reaching the paravertebral venous plexus metastasize to vertebrae, pelvis, and skull. Systemic arterial routes carry malignant tumor cells to these and other distant sites. </div> <bR> <bR> <div> <B> Mechanics of Cancer and Properties of Cancer Cells</B></div> <bR> <bR> <div> <B>(i) Altered Growth Properties</B></div> <div> Malignant cells grow in an uncontrolled and autonomous way. They are practically immortal, e.g. they grow easily in tissue culture.</div> <div> Tumour cells are almost always monoclonal, although subsequently subclones can develop.</div> <div> Tumour cells do not constantly grow at the same rate, but rather grow, stop growing and then start growing again in cycles.</div> <div> Consequently, several factors affect the rate at which a tumour may grow:</div> <bR> <bR> <div> (1) the proportion of malignant cells that have the capacity to divide at the same time</div> <div> (2) the extent of differentiation of the malignant cells; more differentiated cells usually have a decreased capacity to divide. </div> <div> (3) the rate of death of all the malignant cells in the tumour.</div> <div> (4) other factors: blood supply, hormonal susceptibility</div> <bR> <bR> <div> Not all malignant cells differentiate to the same extent. Subclones of malignant cells may possess different properties:</div> <div> * invasiveness.</div> <div> * growth rate / response to growth factors.</div> <div> * metastatic potential.</div> <div> * susceptibility to anticancer drugs or radiotherapy.</div> <div> * the ability to develop resistance to chemo- and/or radiotherapy.</div> <div> * response to hormones e.g. oestrogen receptors in breast cancer.</div> <div> * antigenicity.</div> <bR> <bR> <div> <B>(ii) Karyotypic Changes</B></div> <div> Chromosomal abnormalities. Karyotypic changes may not be detected in all neoplasms or may be difficult to detect. Certain tumours regularly exhibit karyotypic abnormalities:</div> <div> e.g. (I) Philadelphia chromosome (Ph') in chronic myeloid leukaemia (>90% of cases). This is a chromosomal translocation usually from Chr. 9 to Chr. 22 and is of diagnostic use.</div> <div> e.g. (II) Burkitt's lymphoma: translocation of Chr. 8 to 14 in a large % of cases.</div> <div> These karyotypic changes usually represent the abnormal induction of oncogenes, which will be discussed later.</div> <div> Solid tumours such as breast, ovary and colon have been shown to have more random and variable chromosomal abnormalities, although the molecular genetics of neoplasia is still very much in its infancy and more common changes may be discovered in the future.</div> <div> The concept of <I>multistep carcinogenesis</I> involves perhaps 5 or 6 genetic steps. A half dozen genetic steps are believed to be required for neoplastic and subsequent malignant change. At least some of these changes may be associated with phenotypic changes in the cells and tumour. A good example of this concept is provided by a molecular model for the evolution of colorectal cancers, where the normal colonic epithelium goes through 5 morphological changes before becoming a carcinoma (hyperproliferative, 3 types of adenoma and then a carcinoma), each stage correlating with a specific karyotypic change, that will be discussed later under oncogenes.</div> <bR> <bR> <bR> <div> <B>(iii) Antigenic changes</B></div> <div> This provides the basis for immunotherapy, which is still controversial. Tumour-specific antigens (TSAs) are found only on tumour cells while tumour-associated antigens (TAAs) are found on tumour cells and on some normal cells.</div> <div> To date, few TSAs have been found and they are present on only a small proportion of tumours, e.g. 40% of melanomas, 20% of breast cancers and 30% of lung (SCC) cancers express melanoma antigen-1 (MAGE-1) antigen. The discovery of more and more commonly expressed TSAs has obvious potential diagnostic and therapeutic potential.</div> <div> TAAs are of less therapeutic potential but are useful as diagnostic markers. e.g. oncofoetal antigens. <FONT SIZE="3" COLOR="#000000" FACE="Symbol" >a</FONT> -foetoprotein and carcinoembryonic antigen are only normally expressed during foetal development, but may be expressed by neoplastic cells.</div> <bR> <bR> <div> <B>(iv) Metabolic changes</B></div> <div> None of the observed biochemical changes in cancer cells are hallmarks of cancer. The more differentiated neoplastic cells are, the more their biochemical profile (e.g. enzyme content) resembles normal cells. Undifferentiated neoplastic cells have simplified biochemical pathways that allow them to survive and grow under adverse conditions e.g. the patient may be cachexic but the tumour will flourish.</div> <div> Tumour may produce ectopic hormones (some of which will be paraneoplastic effects - see later). Indeed the patient may present with an apparent hormonal abnormality.</div> <bR> <bR> <bR> <div> <B>(v) Cell surface and membrane changes</B></div> <div> The ability of malignant cells to invade, metastasise and cause damage is to a large extent a consequence of cell surface changes. These cell surface changes may be summarised as:</div> <div> (1) The ability to undertake <I>amoeboid movement</I>. Thus, sarcoma cells can move faster than basal cell carcinoma (BCC) cells; sarcomas are more malignant. Malignant cell derived cytokines may promote this movement.</div> <div> (2) Malignant cells are <I>less cohesive</I>; they are easily loosened from each other. Cadherins are Ca2+-dependent cell adhesion molecules (CAMs), that are present on normal cells and hold them together. Some malignant cells down regulate cadherin expression, hence cells are more easily loosened.</div> <div> (3) Malignant cells develop <I>surface receptors</I> that allow them to attach to normal structures and distant tissue, then secrete proteolytic and other enzymes that allow the malignant cells to enter that tissue. The extracellular matrix consists of basement membrane and interstitial connective tissue (collagens, glycoproteins and proteoglycans). Receptor-mediated attachment of malignant cells to laminin and fibronectin receptors allows binding of malignant cells to the basement membrane and extracellular matrix, which is subsequently destroyed by enzymes from the malignant cells. Normal cells express polarised laminin receptors, but malignant cells often overexpress them all over their surface.</div> <div> (4) Malignant cells express <I>enzymes</I> to destroy host tissue, especially extracellular matrix and basement membrane. They may also induce host fibroblasts and macrophages to secrete enzymes. Type IV collagenase (for collagen), and cathepsin D and plasminogen activator (for fibronectin, laminin and protein cores of proteoglycans) are good examples.</div> <div> (5) Malignant cells may <I>secrete growth factors</I> and increase the <I>number of growth factor receptors</I> on their surface to promote their own growth. Mechanisms involved in this process are described in a little more detail in the oncogenes lecture later.</div> <div> (6) Rarely, tumours may release large quantities of <I>coagulation proteins</I> during surgery that result in the development of a hypercoagulation state called disseminated intravascular coagulopathy (DIC). The common carcinomas may rarely do this.</div> <div> (7) Malignant cells are able to <I>transport nutrients and metabolites</I> more easily than normal cells, giving them a growth advantage.</div> <div> (8) Malignant tumours are usually very vascular to support the high rate of growth within the tumour. The production of blood vessels (angiogenesis) is promoted by the release of tumour-associated angiogenesis factors mainly by the tumour cells, but also by inflammatory cells associated with the tumour (macrophages). The factors include FGFs, TGF-<FONT SIZE="3" COLOR="#000000" FACE="Symbol" >a</FONT> and -<FONT SIZE="3" COLOR="#000000" FACE="Symbol" >b</FONT> , EGF, PDGF and vascular endothelial growth factor (VEGF). The expression of many of these factors is a result of the induction of oncogenes (i.e. is part of the neoplastic change in the cell at the genetic level), which will be discussed later.</div> <bR> <bR> <div> <I>[from cornell unversity OI like their explanation of this part:</I></div> <div> <I>T</I><FONT SIZE="3" COLOR="#FF3366" FACE="Arial" ><I>he most fundamental properties of tumor cells are relatively autonomous growth and reproduction and, for malignant tumors, invasion and metastasis. Tumor cells proliferate without relation to the needs of the host in which they arise. Tumor cells are self-controlling and have various levels of independence from normal growth control mechanisms. </I></FONT></div> <div> <I>The normal cell cycle is divisible into four sequential phases that culminate in cell division: the interphase gap (G1), DNA synthesis (S), the gap between the end of DNA synthesis and the beginning of mitosis (G2), and mitosis (M). A fifth interval, G zero, is designated for cells that are no longer in the normal cycle. Some of these cells may be induced to reenter the cycle by appropriate stimuli, and others may never reenter and eventually die. </I></div> <div> <I>In the tumor cell cycle, neoplastic cells may undergo successive cycles of mitosis, or leave the cell cycle and enter G zero. Some of the neoplastic cells in the G zero state will die while others remain as dormant or latent tumor cells and may reenter the cycle of cell division with the appropriate stimulus. </I></div> <div> <I>Normal cells of the body can be divided into several categories: continually replacing cells (hematopoietic tissue, surface epithelium, some glandular epithelium, male germ line); non-renewing cells with regenerative capacity (liver, kidney, connective tissue, some glandular epithelium); and essentially non-replacing cells (neurons, muscle, female germ line). Relevant to the study of neoplastic growth is the category of "continually replacing cells". For example, hematopoietic precursor cells comprise stem cells that are capable of an indefinite number of divisions and progeny cells that either proliferate or mature to a non-proliferative state ("end cells"). As the cells mature toward the "end cell" state, they lose their proliferative potential and gain characteristics of differentiation. In this context, neoplastic growth can be viewed as a disorder of maturation or differentiation in which many of the tumor cells remain in the replicating pool of undifferentiated stem cells. </I></div> <div> <I>The cell growth kinetics of tumor cells and the cell cycle time, from one mitosis to the next, can be measured using radioactive DNA labeling and autoradiography. The cell cycle time of tumor cells varies with cancer type (72-260 hours) and, surprisingly, is often considerably longer than that of normal dividing cells, such as bone marrow precursor cells (18 hours) or colonic crypt epithelial cells (39 hours). The increased frequency of mitosis often seen in malignant tumors is attributed in part to the longer mitotic interval of tumor cells compared to normal cells. </I></div> <div> <I>The "growth fraction" of tumor cells (expressed as percent of tumor cells actually proliferating) and the volume "doubling time" of a tumor can be determined. The growth fraction for common types of human cancers varies widely (5-90%). At the same time, the rate of cell loss from the death of cancer cells may be as much as 90%, or more, of tumor cells per unit time. The true measure of tumor growth is thus the excess of tumor cells produced over those lost per unit time, a value that is reflected in the tumor volume "doubling time". </I></div> <div> <I>The volume-doubling time of individual tumors varies greatly, depending upon histogenetic type, growth fraction, blood supply, and other factors, and may change over time. In general, malignant tumors usually grow more rapidly than benign tumors, undifferentiated malignant tumors grow faster than well differentiated malignant tumors, and carcinoma metastases in lung grow more rapidly than the primary carcinomas from which they have arisen. The doubling time is an indicator of the biological aggressiveness of human tumors. Growth fractions and doubling times of representative human cancers are given in the table. </I></div> <div> <I>Average Growth Fractions and Doubling Times of Human Cancers</I><I> </I></div> <div> <I> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="494" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="226"><div> <I>Human cancer</I></div> </tD> <tD VALIGN=CENTER WIDTH="126"><div> <I>Growth fraction (%)</I></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <I>Doubling time (days)</I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 HEIGHT= 16 WIDTH="486"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="486" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="226"><div> <I>Embryonal tumors</I></div> </tD> <tD VALIGN=CENTER WIDTH="126"><div> <I>90</I></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <I>27</I></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="226"><div> <I>Lymphomas</I></div> </tD> <tD VALIGN=CENTER WIDTH="126"><div> <I>90</I></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <I>29</I></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="226"><div> <I>Sarcomas</I></div> </tD> <tD VALIGN=CENTER WIDTH="126"><div> <I>11</I></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <I>41</I></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 ><NOBR><div> <I>Squamous cell carcinomas</I></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="126"><div> <I>25</I></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <I>58</I></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="226"><div> <I>Adenocarcinomas</I></div> </tD> <tD VALIGN=CENTER WIDTH="126"><div> <I>6</I></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <I>83</I></div> </tD> </tR> </TABLE></I></div> <bR> <div> <I>A theoretical calculation can be made of the number of tumor cell doublings required for the progression from a single transformed cell of 10 micrometer diameter to a 1 cm diameter (~1 gm) solid tumor that is clinically detectable, for example, by chest x-ray. Thirty doublings would be needed to produce a 1 gm tumor, assuming that all of the tumor cells proliferate and none die or are lost. The doubling time is a critical variable in the latency period, the interval between the initiation and clinical expression, of a tumor. Of course, the actual time of occurrence of a tumor-initiating event is seldom known. At a doubling time of about 60 days, approximately 60 months would be required for the tumor to reach a detectable size of ~1 gm. A tumor size of 10 gm would require only 3.3 additional doublings, but the doubling time of a tumor tends to increase as the tumor enlarges. </I></div> <div> <I>The doubling time correlates with the biological aggressiveness of a tumor. In a series of patients with Burkitt's lymphoma, one of the fastest growing human tumors, the clinically determined doubling time of the lymphomas was found to average less than 3 days. By contrast, primary adenocarcinomas of the colon and rectum have an average doubling time of about 600 days.</I><FONT SIZE="2" COLOR="#FF3366" FACE="Arial" ><I>NEOPLASIA</I></FONT></div> <bR> <div> <I>by Robert C. Mellors, M.D., Ph.D.</I><I> </I></div> <bR> <div> <I> ]</I></div> <bR> <div> <I>Clonal Origin and Progression of Tumors</I><FONT SIZE="3" COLOR="#FF3366" FACE="Arial" ><I> </I></FONT></div> <bR> <div> <I>M</I><FONT SIZE="3" COLOR="#FF3366" FACE="Arial" ><I>ost human tumors appear to have a clonal origin and to arise either by clonal expansion of a single transformed cell or by clonal selection of transformed cells having a selective growth advantage. The evidence for tumor monoclonality includes: the presence in a variety of tumors of a single form of certain isoenzymes, such as glucose-6-phosphate dehydrogenase; the production by individual myelomas and B-cell lymphomas of only a single molecular type of immunoglobulin heavy and light chains; </I></FONT></div> <div> <I>and karyotypic similarities, such as the possession of the Philadelphia chromosome by chronic myelogenous leukemia cells. </I></div> <div> <I>Despite their apparent clonal origin, tumor cells within the same lesion often display heterogeneity in several biological characteristics. An explanation of this seeming paradox is found in the stem cell model of cancer which postulates that tumor stem cells have the capacity for self renewal and are responsible for the initial and continuing growth of the tumor. The original clone of tumor cells expands and generates a wide range of variant clones. Depending on selective pressures in the tumor's microenvironment, some subclones survive and expand rapidly while other subclones die out. </I></div> <div> <I>The evolution of tumor-cell heterogeneity is usually accompanied by the development of more aggressive characteristics, such as an increasing growth rate, invasiveness, and metastasis, and by morphological and biochemical changes in the tumor. This entire process is termed "progression" and has important consequences as regards tumor behavior and response to therapy. Examples of tumor progression include the conversion of a benign to a malignant neoplasm, of a non-invasive (in-situ) to an invasive carcinoma, of a low grade to a highly malignant cancer with a rapid fatal course. </I></div> <div> <I>A major factor in progression appears to be that most tumor cells are genetically less stable than normal cells and this instability produces variant clones. Chromosomal abnormalities in number and structure are often seen in tumor cells. These abnormalities include: a gain or loss of chromosomes (aneuploidy); deletion (loss of a segment of a chromosome); inversion ("flip-flop" of two segments of a chromosome); translocation (rearrangement of segments between two chromosomes); and mutation (heritable change in the structure or expression of a gene) ranging from chromosomal change to single base-pair substitution (point mutation). </I></div> <div> <I>Molecular genetic mechanisms implicated in tumor progression include: chromosomal rearrangements or mutations that "activate" cell oncogenes (proto-oncogenes); and loss of putative "tumor suppressor" genes. </I></div> <bR> <bR> <div> <B>Precursor Lesions and Carcinoma in Situ</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b7016800000000.gif" HEIGHT="24" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">I</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B>n mucous membrane sites, where repeated clinical observation and tissue or cell sampling are possible, carcinomas are often seen to be preceded by non-invasive lesions. </B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The epithelial cells of these precursor lesions may have atypical features, among them: enlarged nuclei; somewhat disorderly positional arrangement; and greater than normal proliferative activity. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This abnormal tissue development in the mucosa of the uterine cervix is commonly termed "dysplasia". </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some of the dysplastic lesions may revert to normal, while others progress over time to develop many cellular features of squamous carcinoma except for tissue invasion. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Such an intraepithelial lesion with the cellular features of squamous carcinoma, but remaining confined to the cervical mucosa and not invading through the basement membrane, is termed carcinoma-in-situ. </B></div> <bR> <bR> <div> <B><U>TUMORAL MARKERS:</U></B></div> <bR> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="1001" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 16 WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="131"><div> <I><B> Normal value</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="263"><div> <I><B>First intention marquors</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="197"><div> <I><B>Non specific increased</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="197"><div> <I><B>Other </B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 129 ><NOBR><div> <I><B>CEA [</B></I>Carcinoembryonic Antigen]</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> <10ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Colorectal cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Cirrhosis</div> <div> Renal failure</div> <div> Begign pathology of the lung</div> <bR> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Stomach cancer</div> <div> Liver cancer</div> <div> Thyroid medullary cancer[associated with TCC]</div> <div> Lung cancer</div> <div> Breast  cancer [ CA15-3]</div> <div> Ovary cancer [CA 125]</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 48 WIDTH="197"><div> <I><B>ALPHA-FP</B></I></div> <bR> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 5.5 ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Primary liver cancer</div> <div> Testicular cancer</div> <div> Terato-carcinoma ovarien</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Benign hepatic liver pathology</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="48" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 32 ><NOBR><div> <I><B>BETA2-MICROGLOBULIN</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 3mg/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Multiple myeloma</div> <div> Lymphopathy B</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Tubular disease of the kidney</div> <div> HIV SERO+</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 65 WIDTH="197"><div> <I><B>HCG-BETA </B></I>Human Chorionic Gonadotropin<I><B> ][</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> FREE HCG :10 MU/ML</div> <div> Ultra sensitice HCG :0.1ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Testicular cancer</div> <div> Ovary cancer</div> <div> Placenta tumors</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="65" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="65" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 96 WIDTH="197"><div> <I><B>CA-15-3</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 35 u/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Breast cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Liver cirrhosis</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Cancer of :</div> <div> Ovary</div> <div> Uterus</div> <div> Colorectal</div> <div> Pancreas</div> <div> lung</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 48 WIDTH="197"><div> <I><B>C19-9</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> <65 U/ml pancreas</div> <div> <35 U/ml </div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Pancreas cancer</div> <div> Colorectal cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Pancreatitis</div> <div> Cholestitis</div> <div> cirrhosis</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Stomach cancer</div> <div> Breast cancer</div> <div> Ovary cancer</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 33 WIDTH="197"><div> <I><B>CA-50</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 25 u/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Pancreas cancer</div> <div> Colorectal cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Benign pathology of the ovary and lung</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Ovary</div> <div> Lung</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 16 WIDTH="197"><div> <I><B>CA72-4 [TAG72-B72-3]</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 6 U/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Stomach cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Ovary and colon cancer</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 96 WIDTH="197"><div> <I><B>CA125</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 35 U/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Ovary cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Pancreatitis</div> <div> Cirrhosis</div> <div> Hepathopathies</div> <div> Endometriosis</div> <div> Serous pathology</div> <div> End of pregnancy</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Breast cancer</div> <div> Lung cancer</div> <div> Colon cancer</div> <div> Pancreas cancer</div> <div> Stomach cancer</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 274 WIDTH="197"><div> CA 27-29</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="274" ALIGN="bottom" WIDTH="131" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> breast cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> cancers of </div> <div> the colon, </div> <div> stomach,</div> <div>  kidney, </div> <div> lung, </div> <div> ovary, </div> <div> pancreas, </div> <div> uterus, </div> <div>  liver.disease </div> <div> First trimester pregnancy, </div> <div> endometriosis, </div> <div> ovarian cysts,</div> <div>  benign breast disease, </div> <div> kidney disease,  liver disease are noncancerous conditions that can also elevate CA 27-29 levels.</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> . First trimester pregnancy, </div> <div> endometriosis, </div> <div> ovarian cysts, </div> <div> benign breast disease,</div> <div>  kidney disease,</div> <div>   liver </div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 32 ><NOBR><div> <I><B>NSE [neuron specific enolase]</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 25 ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Bronchitic cancer small cells</div> <div> Neuroblastoma </div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Pheochromocytoma</div> <div> Benign lung disease</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 32 WIDTH="197"><div> <I><B>PAP</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 10 ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Prostate cancer</div> <div> Bone metastasis</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Prostate adenoma</div> <div> Prostatitis </div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 32 WIDTH="197"><div> <I><B>PSA</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> < 10 ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Prostate cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Prostate adenoma</div> <div> Prostatitis</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 64 WIDTH="197"><div> <I><B>SCC or TA4 [Squamous cell carcinoma]</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> <1.5 ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Epithelial uterus cancer</div> <div> Carcinoma epidermoid of the esophagus</div> <div> Lung cancer [epidermoid]</div> <div> Rhinolarhyngo cancer</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> Superior Aerodigestive benign pathology</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="64" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 48 WIDTH="197"><div> <I><B>TCT [thyrocalcitonin]</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><div> <10 ng/ml</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Medullary cancer of the thyroid</div> <div> Endocrine tumors</div> <div> pheochromocytoma</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Chronic renal failure</div> <div> Hyperparathyroidism</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="48" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 64 WIDTH="197"><div> <I><B>TG [thyroglobulin]</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="64" ALIGN="bottom" WIDTH="131" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Differentiate cancer of the thyroid</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Thyroiditis</div> <div> Goiter</div> <div> Basedow</div> <div> Cold nodule of the thyroid</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="64" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 65 WIDTH="197"><div> <I><B>HORMONES</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="65" ALIGN="bottom" WIDTH="131" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> insulin production by islet cell tumor, </div> <div> calcitonin by medullary thyroid carcinoma, </div> <div> catecholamines by pheochromocytoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="65" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> ACTH and ADH by lung cancers</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 49 ><NOBR><div> Galactosyl Transferase II</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="49" ALIGN="bottom" WIDTH="131" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> malignancies, predominantly gastrointestinal</div> <div> pancreatic cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="49" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="49" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 177 WIDTH="197"><div> Lactate Dehydrogenase</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="131"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="177" ALIGN="bottom" WIDTH="131" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Nearly every type of cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="177" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> monitor treatment of some cancers:</div> <div> testicular cancer, </div> <div> Ewing's sarcoma, </div> <div> non-Hodgkin's lymphoma, </div> <div>  some types of leukemia.</div> <div>  Elevated LDH levels caused by: </div> <div> heart failure,</div> <div>  hypothyroidism</div> <div>  anemia, </div> <div>  lung or liver disease</div> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <DIV ALIGN="LEFT"></DIV> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="929" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="217"><div> <I><B>Marker</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="705"><div> <I><B>Tumor</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="923"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="923" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="923"><div> <I><B>Resulting from tumor-cell dedifferentiation</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="923"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="923" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Carcinoembryonic antigen (CEA)</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Carcinomas of gastrointestinal tract, pancreas, breast, lung</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="217"><div> <I><B>Alpha-fetoprotein</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Hepatocellular carcinoma, yolk-sac tumor of testis</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 ><NOBR><div> <I><B>Alkaline phosphatase isoenzyme</B></I></div> <div> <I><B>  (Regan enzyme)</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Various tumors</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="217"><div> <I><B>Ectopic hormones</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Refer to: Paraneoplastic syndromes</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="923"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="923" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFF00 HEIGHT= 16 WIDTH="923"><div> <I><B>Resulting from over-production by tumor cells</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="923"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="923" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Prostate-specific antigen (PSA)</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Prostate carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 ><NOBR><div> <I><B>Choriogonadotropic hormone</B></I></div> <div> <I><B>  (beta subunit)</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Choriocarcinoma, hydatidiform mole, embryonal carcinoma of testis</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="217"><div> <I><B>Calcitonin</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Medullary carcinoma of thyroid</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="217"><div> <I><B>Other Hormones</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Refer to: Endocrine tumors</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="217"><div> <I><B>Myeloma and Bence-Jones proteins</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Multiple myeloma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Monoclonal macroglobulinemia</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="705"><div> Waldenstrom's macroglobulinemia</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="923"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="923" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <B><U>http://edcenter.med.cornell.edu/CUMC_PathNotes/Neoplasia/Neoplasia_09.html</U></B><B>Robert C. Mellors, M.D., Ph.D.</B></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="415" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="110"><div> <I><B>Disease</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="298"><div> <I><B>Marker</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP ROWSPAN=7 BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Colorectal Cancer</B></I></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> Serum CEA</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> Serum LASA</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> Serum CA 19-9</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> DNA flow cytometric ploidy (DNA index)</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> DNA flow cytometric proliferation index (% S phase)</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> p53 Tumor suppressor gene</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> ras oncogene</div> </tD> </tR> <tR> <tD VALIGN=TOP ROWSPAN=8 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="110"><div> <I><B>Breast</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> Serum CA 15-3</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> Serum CEA (carcinoembryonic antigen)</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> Estrogen and progesterone receptors</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> DNA flow cytometric ploidy (DNA index)</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> DNA flow cytometric proliferation index (% S phase)</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> p-53 Tumor supressor gene</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> c-erbB-2</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="298"><div> Cathepsin-D</div> </tD> </tR> </TABLE></div> <bR> <div> <B>Hormone Production by Human Tumors </B></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="782" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="151"><div> <I><B>Tissue</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="168"><div> <I><B>Tumor</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="187"><div> <I><B>Hormone</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="263"><div> <I><B>Clinical Features</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="772"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="772" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 BGCOLOR=#FFFF00 HEIGHT= 16 WIDTH="772"><div> <I><B>Hormones appropriate for the tumor tissue of origin (endocrine tumors): </B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="151"><div> <I><B>Adrenal Cortex</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Adenoma,</div> <div> carcinoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> Cortisol</div> <div> Aldosterone</div> <div> Androgen</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Cushing's syndrome</div> <div> Conn's syndrome</div> <div> Adrenogenital syndrome</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="151"><div> <I><B>Adrenal Medulla</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Pheochromo-cytoma</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> Norepinephrine,</div> <div> epinephrine</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Hypertension</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="151"><div> <I><B>Pancreas Islet</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Adenoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> Insulin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Hypoglycemia, </div> <div> hyperinsulinism</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="151"><div> <I><B>Enterochromaffin</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Carcinoid</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> Serotonin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Carcinoid syndrome </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="151"><div> <I><B>Placenta</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Choriocarcinoma,</div> <div> hydatidiform mole</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> Gonadatropin </div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="263" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 BGCOLOR=#FFFF00 HEIGHT= 32 WIDTH="772"><bR> <div> <I><B>Ectopic hormones, inappropriate for tumor tissue of origin (non-endocrine tumors): </B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="151"><div> <I><B>Lung</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Oat cell carcinoma</div> <bR> <div> Squamous cell</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> ACTH</div> <div> ADH</div> <div> PTH-like</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Cushing's syndrome</div> <div> Inappropriate diuresis</div> <div> Hypercalcemia</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="151"><div> <I><B>Kidney</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Adenocarcinoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> PTH-like</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Hypercalcemia </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="151"><div> <I><B>Liver</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Hepatoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> Gonadatropin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Precocious puberty,</div> <div> gynecomastia</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="151"><div> <I><B>Lung</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="168"><div> Oat cell carcinoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="187"><div> Gonadotropin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="263"><div> Gynecomastia</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="772"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="772" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <B>Cellular Growth Factors </B></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="773" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=BOTTOM BGCOLOR=#800000 HEIGHT= 33 WIDTH="161"><div> <I><B>Factor</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="111"><div> <I><B>Full Name</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="41"><div> <I><B>Size (kD)</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="163"><div> <I><B>Source</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="281"><div> <I><B>Target Cell</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=5 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="761"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="761" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="161"><div> <I><B>EGF</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Epidermal</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 6</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Salivary gland</div> <div> GI cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Many epithelial and mesenchymal cells</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="161"><div> <I><B>TGF-A</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Transforming</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 5.6</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Tumor cells</div> <div> Placenta & embryos</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Same</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="161"><div> <I><B>PDGF</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Platelet derived</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 32</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Platelets</div> <div> Endothelium</div> <div> Placenta</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Mesenchymal cells</div> <div> Smooth muscle</div> <div> Trophoblast</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 64 WIDTH="161"><div> <I><B>TGF-B</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Transforming</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 25</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Platelets</div> <div> Tumor cells</div> <div> Kidney</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Fibroblasts</div> <div> Keratinocytes</div> <div> Mammary cells</div> <div> Carcinoma cells</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="161"><div> <I><B>IGF1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Insulin-like (Somatomedin C)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 7</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Liver</div> <div> Smooth muscle</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Epithelial and mesenchymal cells</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="161"><div> <I><B>IGF2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Insulin-like (Somatomedin A)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 7</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Fetal liver</div> <div> Placenta</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Same</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="161"><div> <I><B>IL2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Interleukin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 15</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> T-helper cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> T-lymphocytes</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="161"><div> <I><B>FGF</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Fibroblast</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 16</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Brain, Tumors,</div> <div> Salivary gland</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Endothelial cells</div> <div> Fibroblasts</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="161"><div> <I><B>CSF1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Colony Stimulating (macrophage)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 70</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> L-cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Macrophage precursors</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="161"><div> <I><B>CSF2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> (macrophage-granulocytic)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 15-28</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Lung</div> <div> Placenta</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Macrophage & granulocyte precursors</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="161"><div> <I><B>CSF3</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> MultiCSF (IL3)</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 28</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> T-lymphocytes</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> Many types of leukocytes</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="161"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="161" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="111"><div> Bombesin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="41"><div> 2</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="163"><div> Brain</div> <div> GI cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="281"><div> CNS, GI tract</div> <div> Oat cell carcinoma</div> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <bR> <div> TUMOR SUPPRESSOR GENES</div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="582" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#800000 HEIGHT= 19 WIDTH="58"><div> <I>GENE</I></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000><NOBR><div> <I><B>CHROMOSOME</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="373"><div> <I><B>ASSOCIATED TUMOR</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="58"><div> <I><B>VHL</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 3p</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Renal cell carcinoma</div> <div> Von hippel-lindau disease</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="58"><div> <I><B>APC</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 5q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Colorectal carcinoma</div> <div> Familial adenomatous polyposis coli</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="58"><div> <I><B>WT-1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 11p</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Wilm's tumor</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="58"><div> <I><B>Rb</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 13q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Retinoblastoma </div> <div> osteosarcoma</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 ><NOBR><div> <I><B>BRCA-2</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 13q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Breast cancer</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="58"><div> <I><B>P53</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 17p</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Most human cancer</div> <div> li-Fraumeni syndrome</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="58"><div> <I><B>NF-1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 17q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Neurofibromatosis type I</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 ><NOBR><div> <I><B>BRCA-1</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 17q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> BREAST CANCER</div> <div> OVARIAN CANCER</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="58"><div> <I><B>DCC</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 18q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Carcinoma of the colon and stomach</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="58"><div> <I><B>DPC</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 18q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="373"><div> Pancreatic cancer</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="58"><div> <I><B>NF-2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="141"><div> 22q</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Neurofibromatosis type II [BILATERAL ACOUSTIC NEUROMA]</div> </NOBR></tD> </tR> </TABLE></div> <bR> <bR> <bR> <div> <B>ONCOGENES GROWTH PROMOTING GENES:</B></div> <bR> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="578" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#800000 HEIGHT= 35 WIDTH="158"><div> <I><B>FUNCTIONAL CATEGORY</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000><NOBR><div> <I><B>ONCOGENE</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="174"><div> <I><B>ACTION</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="127"><div> <I><B>TUMORS</B></I></div> </tD> </tR> </TABLE></div> <div> <B> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="578" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="HSIDES" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 ><NOBR><div> <I><B>GROWTH FACTOR</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="106"><div> Sis </div> <div> int,hst</div> <bR> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="174"><div> PDGF truncated</div> <div> FGF like</div> <bR> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Glioma</div> <div> Breast,esophagus</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 44 WIDTH="158"><div> <I><B>GROWTH FACTOR RECEPTOR</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="106"><div> Erb-B</div> <div> Erb-B2</div> <div> Her2/neu</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="174"><div> EGFR</div> <div> EGFR-LIKE</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="127"><div> Breast, ovary</div> <bR> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 104 WIDTH="158"><div> <I><B>SIGNAL TRANSDUCTION/ RELAY FACTORS</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="106"><div> Ret</div> <div> Scr</div> <div> Abl</div> <bR> <div> N-ras</div> <div> Ki-ras</div> <bR> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="174"><bR> <div> Tyrosine Kinase</div> <bR> <bR> <div> GPT binding</div> <div> GPT binding</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="127"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="104" ALIGN="bottom" WIDTH="127" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 60 WIDTH="158"><div> <I><B>TRANSCRIPTION FACTORS</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="106"><div> c-myc</div> <div> n-myc</div> <div> L-myc</div> <bR> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="174"><div> Activating growth promoting genes</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="127"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="60" ALIGN="bottom" WIDTH="127" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 60 ><NOBR><div> <I><B>CELL CYCLE CONTROL</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="106"><div> Bcl-1</div> <div> [PRADI]</div> <div> mdm-2</div> <bR> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="174"><div> Codes cyclin -D1</div> <bR> <div> P53 antagonist</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="127"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="60" ALIGN="bottom" WIDTH="127" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 ><NOBR><div> <I><B>APOPTOSIS BLOCK</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="106"><div> Bcl-2</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="174"><div> Inhibits programmed cell death</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="127"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="33" ALIGN="bottom" WIDTH="127" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></B></div> <bR> <bR> <div> Oncogenic viruses</div> <bR> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="563" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#800000 HEIGHT= 24 WIDTH="318"><div> <I><B>virus</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000><NOBR><div> <I><B>Associated cancer</B></I></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 30 WIDTH="318"><bR> <div> <I><B>HTLV-1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="238"><bR> <div> ADULT T- CELL LEUKEMIA</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 30 WIDTH="318"><bR> <div> <I><B>HBV</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="238"><bR> <div> HEPATOCELLULAR CARCINOMA</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 43 WIDTH="318"><bR> <div> <I><B>EBV</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><bR> <div> BURKITT'S LYMPHOMA</div> <div> NASOPHARYNGEAL CARCINOMA</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 43 WIDTH="318"><bR> <div> <I><B>HPV</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="238"><bR> <div> CERVICAL CARCINOMA</div> <div> PENILE\ANAL CARCINOMA</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 30 ><NOBR><bR> <div> <I><B>HHV8 [KAPOSI'S SARCOMA ASSOCIATED HERPESVIRUS]</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="238"><bR> <div> KAPOSI'S SARCOMA</div> </tD> </tR> </TABLE></div> <bR> <bR> <div> <B>Cellular Functions of Protooncogene Encoded Proteins</B> </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="455" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 49 WIDTH="131"><div> <I><B>Function</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="80"><div> <I><B>Protein</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="60"><div> <I><B>Protoonco-</B></I></div> <div> <I><B>gene</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000><NOBR><div> <I><B>Associated Human Cancers</B></I></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=4 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="445"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="445" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="131"><div> <I><B>Growth factor</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="80"><div> PDGF</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="60"><div> sis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="171"><div> Osteosarcoma</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="131"><div> <I><B>Growth-factor receptor</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> EGF receptor</div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="60"><div> erb B</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> Breast, lung, ovarian cancer</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="131"><div> <I><B>Post-receptor signal transduction</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="80"><div> GTP-binding protein</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="60"><div> ras</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="171"><div> Lung, colon, pancreatic cancer</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="131"><div> <I><B>Nuclear transcription regulator</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> myc protein</div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="60"><div> myc</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="171"><div> Breast, colon, lung cancer, Burkitt's lymphoma</div> </tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=4 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="445"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="445" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <bR> <div> <B>Proteins Encoded by Proto-oncogenes and DNA Tumor Viruses</B> </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="454" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 ><NOBR><div> <I><B>Localization</B></I></div> </NOBR></tD> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#800000 WIDTH="345"><div> <I><B>Proteins Encoded by</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> Cellular Proto-oncogene</div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><div> DNA Tumor Virus</div> </tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="446"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="446" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><div> <I><B>Nuclear</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> myc</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><div> SV40 large T</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> N-myc</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><div> Polyoma large T</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> myb</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><div> Adenovirus E1a</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Cytoplasmic</B></I></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> ras</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><div> Polyoma middle T</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> abl</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="150" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> src</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="150" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> erb B</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="150" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="100"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="100" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="194"><div> sis</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="150"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="150" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <bR> <div> <B>Cellular Functions of Oncogene-Encoded Proteins</B> </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="484" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="191"><div> <I><B>Function</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="91"><div> <I><B>Protein</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000><NOBR><div> <I><B>Proto-oncogene (Oncogene)</B></I></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="476"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="476" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="191"><div> <I><B>Growth factor</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="91"><div> PDGF</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="192"><div>     sis</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Growth-factor receptor</B></I></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> EGF receptor</div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="192"><div>     erb B</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Non-receptor protein kinase</B></I></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="91"><div> pp60src</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="192"><div>     src</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="191"><div> <I><B>GTP-binding protein</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="91"><div> p21ras</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="192"><div>     H-ras</div> </tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="476"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="476" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <bR> <div> <B>Cellular Genes Associated with Human Cancer Susceptibility and Expression</B> </div> <div> <B>Human Genes Associated with Cancer Susceptibility and Expressions</B> </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="454" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="133"><div> <I><B>Affected Gene</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000><NOBR><div> <I><B>Chromosome</B></I></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="240"><div> <I><B>Associated Cancer</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="446"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="446" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>Oncogenes:</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="71" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="240" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>abl</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 9(q24)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Chronic myeloid leukemia</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>c-myc</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 8(q24)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Burkitt's lymphoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="133"><div> <I><B>ras</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 12(p)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Variety of cancers: colon, lung, pancreas, leukemia</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>N-myc</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 2(p)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Neuroblastoma, small cell cancer of lunh</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="133"><div> <I><B>RET</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 10(q11)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Medullary thyroid carcinoma, multiple endocrine neoplasias</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>PML/RAR-alpha</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> t(15;17)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Acute promyelocytic leukemia</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="133"><div> <I><B>Tumor Suppressor Genes:</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="33" ALIGN="bottom" WIDTH="71" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="33" ALIGN="bottom" WIDTH="240" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>APC</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 5(q21)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Colon carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>BRCA 1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 17(q21)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Breast and ovarian carcinoma</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>BRCA 2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> 13(q12-13)</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Breast carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>p53</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 17(p13)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Variety of cancers, Li-Fraumeni syndrome</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>NF1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 17(q11)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Neurofibromatosis type 1</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>RB</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 13(q14)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Retinoblastoma, osteosarcoma</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>WT1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 11(p13)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Wilms' tumor</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="133"><div> <I><B>Mismatch Repair Genes:</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="33" ALIGN="bottom" WIDTH="71" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="33" ALIGN="bottom" WIDTH="240" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="133"><div> <I><B>hMSH2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="71"><div> 2(p16)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="240"><div> Colon carcinoma</div> </tD> </tR> </TABLE></div> <bR> <bR> <div> <B>Cellular Growth Factors </B></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="573" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=BOTTOM BGCOLOR=#800000 HEIGHT= 16 WIDTH="103"><div> <I><B>Factor</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="118"><div> <I><B>Full Name</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000><NOBR><div> <I><B>Size (kD)</B></I></div> </NOBR></tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="122"><div> <I><B>Source</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="155"><div> <I><B>Target Cell</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=5 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="561"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="561" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="103"><div> <I><B>EGF</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Epidermal</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 6</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> Salivary gland</div> <div> GI cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> Many epithelial and mesenchymal cells</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="103"><div> <I><B>TGF-A</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Transforming</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 5.6</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Tumor cells</div> <div> Placenta & embryos</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> Same</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 48 WIDTH="103"><div> <I><B>PDGF</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Platelet derived</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 32</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> Platelets</div> <div> Endothelium</div> <div> Placenta</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Mesenchymal cells</div> <div> Smooth muscle</div> <div> Trophoblast</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 64 WIDTH="103"><div> <I><B>TGF-B</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Transforming</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 25</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> Platelets</div> <div> Tumor cells</div> <div> Kidney</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> Fibroblasts</div> <div> Keratinocytes</div> <div> Mammary cells</div> <div> Carcinoma cells</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="103"><div> <I><B>IGF1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Insulin-like (Somatomedin C)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 7</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Liver</div> <div> Smooth muscle</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> Epithelial and mesenchymal cells</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="103"><div> <I><B>IGF2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Insulin-like (Somatomedin A)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 7</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> Fetal liver</div> <div> Placenta</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> Same</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="103"><div> <I><B>IL2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Interleukin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 15</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> T-helper cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> T-lymphocytes</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="103"><div> <I><B>FGF</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Fibroblast</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 16</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> Brain, Tumors,</div> <div> Salivary gland</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> Endothelial cells</div> <div> Fibroblasts</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="103"><div> <I><B>CSF1</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Colony Stimulating (macrophage)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 70</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> L-cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Macrophage precursors</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="103"><div> <I><B>CSF2</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> (macrophage-granulocytic)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 15-28</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> Lung</div> <div> Placenta</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> Macrophage & granulocyte precursors</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="103"><div> <I><B>CSF3</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> MultiCSF (IL3)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 28</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> T-lymphocytes</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Many types of leukocytes</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="103"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="103" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="118"><div> Bombesin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="59"><div> 2</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="122"><div> Brain</div> <div> GI cells</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="155"><div> CNS, GI tract</div> <div> Oat cell carcinoma</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=5 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="561"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="561" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <div> <B>Occupational Cancers</B> </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="570" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="203"><div> <I><B>Agent</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="197"><div> <I><B>Occupation</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="160"><div> <I><B>Cancer Site</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="562"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="562" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="203"><div> <I><B>Ionizing radiations</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="197" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="160" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="203"><div> <I><B>radon</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> certain underground miners (uranium, fluorspar,etc.)</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> bronchus</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="203"><div> <I><B>X-rays, radium</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> radiologists, radiographers</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> skin</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="203"><div> <I><B>radium</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> luminous dial painters</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> bone </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="203"><div> <I><B>Ultraviolet radiation</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> farmers, sailors, etc.</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> skin</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 49 WIDTH="203"><div> <I><B>Polycyclic hydrocarbons in soot, tar, oil</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> chimney sweepers, manufacturers of coal gas, many other groups of exposed industrial workers</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> scrotum, skin, bronchus</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="203"><div> <I><B>2-Naphthylamine; 1-naph-thylamine</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> chemical workers, rubber workers, manufacturers of coal gas</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> bladder</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Benzidine; 4-aminobiphenyl</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> chemical workers</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> bladder</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="203"><div> <I><B>Asbestos</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> asbestos workers, shipyard and insulation workers</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> bronchus, pleura, and peritoneum</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 49 WIDTH="203"><div> <I><B>Arsenic</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> sheep dip manufacturers, gold miners, some vineyard workers and ore smelters</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> skin and bronchus</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Bis(chloromethyl) ether</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> makers of ion-exchange resins</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> bronchus</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="203"><div> <I><B>Benzene</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> workers with glues, varnishes, etc.</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> marrow (leukemia)</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="203"><div> <I><B>Mustard gas</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> poison gas makers</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="160"><div> bronchus, larynx, nasal sinuses</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="203"><div> <I><B>Vinyl chloride</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="197"><div> PVC manufacturers</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> liver (angio-sarcoma)</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="562"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="562" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <div> <B>Major Chemical Carcinogens</B> </div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="586" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#800000 HEIGHT= 49 WIDTH="290"><div> <B>Pro-carcinogens</B></div> <div> <B> (require metabolic activation to "ultimate carcinogens")</B></div> </tD> <tD VALIGN=TOP BGCOLOR=#800000 WIDTH="289"><div> <I><B>Direct-Acting Carcinogens </B></I></div> <div> <I><B>(DNA-reactive)</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 546 WIDTH="290"><div> <B>Polycyclic aromatic hydrocarbons </B></div> <div> <B>benzanthracene (first pure carcinogen) </B></div> <div> <B>3,4-benzpyrene (isolated from coal tar) </B></div> <div> <B>3-methylcholanthrene (prepared from a steroid, deoxycholic acid) </B></div> <div> <B>7,12-dimethylbenzanthracene (most potent carcinogen)</B></div> <div> <B>Aromatic Amines and Azo Dyes </B></div> <div> <B>2-naphtylamine (produces bladder carcinoma) </B></div> <div> <B>benzidine (produces bladder carcinoma) </B></div> <div> <B>2-acetylaminofluorene </B></div> <div> <B>4-dimethylaminoazobenzene (produces liver tumors)</B></div> <div> <B>Natural Products </B></div> <div> <B>aflatoxin B1 (potent hepatocarcinogen produced by mold contamination of food) </B></div> <div> <B>mitomycin C </B></div> <bR> <div> <B>Other </B></div> <div> <B>nitrosamine (can be formed by action of nitrites on foods) </B></div> <div> <B>some insecticides (chlordane and others) </B></div> <div> <B>some metals (chromium and nickel) </B></div> <div> <B>carbon tetrachloride</B></div> <bR> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="289"><div> <B>Alkylating agents </B></div> <div> <B>anticancer chemotherapeutic drugs (cyclophosphamide, busulfan, chlorambucil) </B></div> <div> <B>beta-propiolactone </B></div> <div> <B>bis(chloromethyl)ether</B></div> <div> <B>Acetylating agents </B></div> <div> <B>1-acetylimidazole</B></div> </tD> </tR> </TABLE></div> <bR> <div> <B>Latent Periods of Representative Occupational Cancers</B> </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="564" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="127"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="127" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="88"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="88" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="121"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="121" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#800000 WIDTH="213"><div> <I><B>LatentPeriod (years)</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FFFF HEIGHT= 16 WIDTH="127"><div> <I><B>Site of Cancer</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF><NOBR><div> Type of Cancer</div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="121"><div> Agent</div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="82"><div> Average</div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="130"><div> Range</div> </tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=5 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="552"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="552" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 64 WIDTH="127"><div> <I><B>Skin</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="88"><div> Epidermoid and basal cell carcinomas</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Arsenic</div> <div> Coal tar & pitch</div> <div> Ionizing radiation</div> <div> Solar radiation</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> 25</div> <div> 20-24</div> <div> 7</div> <div> 20-30</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> 4-46</div> <div> 1-50</div> <div> 1-12</div> <div> 15-40</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="127"><div> <I><B>Lung</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="88"><div> Bronchogenic carcinoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Asbestos</div> <div> Ionizing radiation</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> 18</div> <div> 25-35</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> 15-48</div> <div> 7-50</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="127"><div> <I><B>Bone marrow</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="88"><div> Leukemia</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Benzene</div> <div> Ionizing radiation</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="32" ALIGN="bottom" WIDTH="82" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> 3-19</div> <div> 3-15</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="127"><div> <I><B>Bladder</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="88"><div> Squamous cell carcinoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Aromatic amines</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> 11-15</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> 2-40</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="127"><div> <I><B>Bone</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="88"><div> Osteogenic sarcoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Ionizing radiation</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="33" ALIGN="bottom" WIDTH="82" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> 10-25</div> </tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=5 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="552"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="552" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <bR> <bR> <div> <B>Hereditary Cancers and Inherited Disease Syndromes Associated with a High Incidence of Cancer (Short List)</B> </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="685" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="254"><div> <I><B>Disease/Syndrome</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="291"><div> <I><B>Associated Neoplasm</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="130"><div> <I><B>Inheritance</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="677" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="254"><div> <I><B>Breast/Ovarian</B></I></div> <div> <I><B>Cancer Syndrome</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><div> Early onset breast cancer/</div> <div> ovarian cancer</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><div> D </div> </tD> </tR> <tR> <tD VALIGN=BOTTOM COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><div> <I><B>Chromosomal Instability Syndromes:</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Bloom's syndrome</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Leukemia, intestinal cancer</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> R</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Fanconi's anemia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Leukemia, squamous carcinoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> R</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="254" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=BOTTOM COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><div> <I><B>Hereditary Skin Diseases:</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Xeroderma pigmentosa</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Skin cancers</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> R</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="254" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=BOTTOM COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><div> <I><B>Endocrine System:</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Multiple endocrine neoplasia</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Adenomas of endocrine glands</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Zollinger-Ellison syndrome</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Pancreatic & duodenal gastrinomas</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="254" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=BOTTOM COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><div> <I><B>Nervous System:</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Retinoblastoma</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Retinoblastoma, bilateral</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Neuroblastoma</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Pheochromocytoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> R</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="254"><div> <I><B>Neurofibromatosis</B></I></div> <div> <I><B>(von Recklinghausen's)</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Fibrosarcoma, meningioma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="254" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=BOTTOM BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Gastrointestinal System:</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=BOTTOM BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Familial polyposis coli</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Interstinal polyps and carcinomas</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Gardener's syndrome</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Intestinal polyps & cancers, osteomas</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="254" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=BOTTOM COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><div> <I><B>Vascular System:</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Osler-Weber-Rendu syndrome</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Angioma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Ataxia-telangiectasia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Lymphoma, leukemia, gastric cancer</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> R</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="254" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=BOTTOM COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><div> <I><B>Urogenital System:</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Wilms' tumor</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D & R</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>Stein-Leventhal syndrome</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Endometrial carcinoma</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="254" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="291"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="291" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=BOTTOM COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><div> <I><B>Immunologic Syndromes:</B></I></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Agammaglobulinemia (Swiss type)</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Lymphoma, leukemia</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> R</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>X-linked agammaglobulin- </B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="291"><div> Lymphoma, leukemia</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> XR</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="254"><div> <I><B>DiGeorge syndrome</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Squamous carcinoma of upper respiratory tract</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="130"><div> D</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="677"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="677" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Mode of inheritance: D, autosomal dominant; R, autosomal recessive; XR, X-linked recessive.</B></I></div> </NOBR></tD> </tR> </TABLE></div> <DIV ALIGN="LEFT"></DIV> <div> <A HREF="http://edcenter.med.cornell.edu/CUMC_PathNotes/Neoplasia/Neoplasia_07.html" TARGET="_top" TITLE="http://edcenter.med.cornell.edu/CUMC_Pat"><U><U>http://edcenter.med.cornell.edu/CUMC_PathNotes/Neoplasia/Neoplasia_07.html</U></U></A></div> <div> <B>Robert C. Mellors, M.D., Ph.D</B></div> <bR> <bR> <div> <B>Severe Infections in Patients with Cancer </B></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="676" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 16 WIDTH="255"><div> <I><B>Bacterial</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="90"><div> <I><B>Fungal</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="94"><div> <I><B>Parasitic</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#800000 WIDTH="224"><div> <I><B>Viral</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="666"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="666" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="255"><div> <I><B>Pyogenic cocci</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="90"><div> Candidiasis</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Pneumocystosis</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="224"><div> Cytomegalovirus</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 32 WIDTH="255"><div> <I><B>Gram-negative septicemia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Cryptococcosis</div> <div> Histoplasmosis</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Toxoplasmosis</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="224"><div> Herpes simplex</div> <div> Herpes zoster</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="255"><div> <I><B>Tuberculosis</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Aspergillosis</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="94"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="94" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="224"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="224" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="255"><div> <I><B>Nocardiosis</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="90"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="90" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="94"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="94" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="224"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="224" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <B>Some Paraneoplastic Syndromes</B></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="675" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=BOTTOM BGCOLOR=#800000 HEIGHT= 16 WIDTH="228"><div> <I><B>Endocrine Syndromes</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="82"><div> <I><B>Hormone</B></I></div> </tD> <tD VALIGN=BOTTOM BGCOLOR=#800000 WIDTH="355"><div> <I><B>Tumor Type</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="667"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="667" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="228"><div> <I><B>Cushing's syndrome</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> ACTH</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Oat (small)-cell carcinoma of lung, thymoma, pancreatic carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Inappropriate diuresis</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> ADH</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Oat-cell carcinoma of lung, intracranial tumors</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Gynecomastia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> HCG</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Oat-cell carcinoma of lung, rarely liver tumors</div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="228"><div> <I><B>Hypercalcemia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> PTH-like</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Squamous cell carcinoma of lung, breast carcinoma, renal carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Hypocalcemia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> Calcitonin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Breast carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Hypoglycemia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> Insulin-like</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Fibrosarcoma, other sarcomas</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Carcinoid syndrome</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> Serotonin</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Carcinoid tumors,pancreatic carcinoma, </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Polycythemia</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC><NOBR><div> Erythropoietin</div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Renal and liver carcinomas</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="667"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="667" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 16 WIDTH="228"><div> <I><B>Other syndromes</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="82"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="82" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="355"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="355" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="667"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="667" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Dermatomyositis</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Carcinoma of lung, ovary, breast</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Acanthosis nigrans</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Gastric carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Hypertrophic osteo-arthropathy</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Bronchogenic carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Migratory venous thrombosis</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Pancreatic carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Myasthenia gravis</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Thymoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 ><NOBR><div> <I><B>Autoimmune hemolytic anemia</B></I></div> </NOBR></tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Chronic lymphocytic leukemia</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="228"><div> <I><B>Renal dysfunction</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Multiple myeloma, colon carcinoma</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="228"><div> <I><B>Disseminated intravascular coagulation (DIC)</B></I></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="82"><div> None</div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFCC WIDTH="355"><div> Advanced cancers</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="667"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="667" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=3 BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="667"><div> <I><B>Symbols: ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; HCG, human choriogonadotropic hormone; PTH-like, parathormone-like.</B></I></div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="665" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BELOW" RULES="ROWS" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=3 BGCOLOR=#800000 HEIGHT= 16 WIDTH="657"><div> <I><B>Common Malignant Neoplasms Of Infancy and Childhood</B></I></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>0 to 4 years</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> 5 to 9 years</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><div> 10 to 14 years</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>Leukemia</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> Leukemia</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="149" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>Retinoblastoma</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> Retinoblastoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="149" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>Retinoblastoma</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> Retinoblastoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="149" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>Wilms' Tumor</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="187" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="149" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>Hepatoblastoma</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> Hepatocarcinoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><div> Hepatocarcinoma</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 33 WIDTH="319"><div> <I><B>Soft Tissue Carcinoma (especially rhabdomyosarcoma)</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> Soft Tissue Carcinoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> Soft Tissue Carcinoma</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>Teratomas</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="187" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="149" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><div> <I><B>Central Nervous System Tumors</B></I></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> Central Nervous System Tumors</div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="149" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="319" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> Ewing Sarcoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="149" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="319" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><div> Lymphoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC><NOBR><div> Osteogenic sarcoma</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="319" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="187" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><div> Thyroid carcinoma</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFCC HEIGHT= 16 WIDTH="319"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="319" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="187"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="187" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFFCC WIDTH="149"><div> Hodgkin disease</div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="513" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#FF0000 HEIGHT= 30 ><NOBR><div> <B>Diagnostic Methods for Neoplasia </B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="92"><div> <B>Method </B></div> </tD> <tD VALIGN=CENTER WIDTH="406"><div> <B>Application </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 96 WIDTH="92"><div> <B>History and Physical Examination</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="406"><div> What the health care worker learns from talking to the patient and through direct examination may give clues to the presence of a neoplasm. Signs and symptoms such as weight loss, fatigue, and pain may be present. A mass may be palpable or visible. </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 115 WIDTH="92"><div> <B>Radiographic Techniques</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FF00 WIDTH="406"><div> The use of plain films (x-rays), computed tomography (CT), magnetic resonance imaging (MRI), mammography, and ultrasonography (US) may be very helpful to detect the presence and location of mass lesions. The findings from these methods may aid in staging and determination of therapy. </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 191 WIDTH="92"><div> <B>Laboratory Analyses</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="406"><div> General findings such as anemia, enzyme abnormalities (such as an increased alkaline phosphatase), and hematuria or positive stool occult blood are helpful to suggest further workup. More specific testing, such as measurement of prostate specific antigen levels, may help to determine the presence of specific neoplasms, but such tests are not perfect screening tools in a general population. Detection of specific genes (such as BRCA-1 for breast cancer) may suggest an increased risk for some malignancies. </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 115 ><NOBR><div> <B>Cytology</B> </div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#0000FF WIDTH="406"><div> Methods that sample cells can be simple and cost-effective and minimally invasive. A good example is the Pap smear for diagnosis of cervical dysplasias and neoplasms. Cells exfoliated into body fluids may also be examined. Fine needle aspiration (FNA) can be used to sample a variety of mass lesions. </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 153 WIDTH="92"><div> <B>Tissue Biopsy and Surgery</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="406"><div> Methods that sample small pieces of tissue (biopsy) from a particular site, often via endoscopic techniques (such as colonoscopy, upper endoscopy, or bronchoscopy) can often yield a specific diagnosis of malignancy. At surgery, portions of an organ or tissue can be sampled, or the diseased tissue(s) removed and examined in surgical pathology to determine the stage and grade of the neoplasm. </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 153 ><NOBR><div> <B>Autopsy</B> </div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="406"><div> Sometimes neoplasms are not detected or completely diagnosed during life. The autopsy serves as a means of quality assurance for clinical diagnostic methods, as a way of confirming diagnoses helpful in establishing risks for family members, as a means for gathering statistics for decision making about how to approach diagnosis and treatment of neoplasms, and to provide material for future research. </div> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <bR> </td> </tr></table></body>