<?xml version="1.0" encoding="ISO-8859-1"?><cms:container xmlns:cms="http://edoc.hu-berlin.de/diml/module/cms"><cms:document><cms:meta><cms:entry id="front" part="front" ref="front" type="front"/><cms:entry type="title">Immunhistologische Untersuchungen an primären Melanomen und deren Metastasen mit SM5-1, einem neuen monoklonalen Antikörper</cms:entry><cms:entry type="author">Susanne Reinke</cms:entry><cms:entry id="chapter1" part="chapter1" ref="chapter1" type="chapter">1.</cms:entry><cms:entry id="N1005F" part="chapter1" ref="N1005F" type="pagenumber">1</cms:entry><cms:entry id="N10064" part="chapter1" ref="N10064" type="section">1.1</cms:entry><cms:entry id="N10073" part="chapter1" ref="N10073" type="section">1.2</cms:entry><cms:entry id="N1008F" part="chapter1" ref="N1008F" type="pagenumber">2</cms:entry><cms:entry id="N100CB" part="chapter1" ref="N100CB" type="section">1.3</cms:entry><cms:entry id="N100CF" part="chapter1" ref="N100CF" type="pagenumber">3</cms:entry><cms:entry id="N100DE" part="chapter1" ref="N100DE" type="section">1.4</cms:entry><cms:entry id="N100EA" part="chapter1" ref="N100EA" type="section">1.5</cms:entry><cms:entry id="N100FA" part="chapter1" ref="N100FA" type="pagenumber">4</cms:entry><cms:entry id="N10110" part="chapter1" ref="N10110" type="section">1.6</cms:entry><cms:entry id="N10123" part="chapter1" ref="N10123" type="table"/><cms:entry id="N1012A" part="chapter1" ref="N1012A" type="pagenumber">5</cms:entry><cms:entry id="N101BF" part="chapter1" ref="N101BF" type="table"/><cms:entry id="N1026C" part="chapter1" ref="N1026C" type="table"/><cms:entry id="N10273" part="chapter1" ref="N10273" type="pagenumber">6</cms:entry><cms:entry id="N10419" part="chapter1" ref="N10419" type="table"/><cms:entry id="N10420" part="chapter1" ref="N10420" type="pagenumber">7</cms:entry><cms:entry id="N105F3" part="chapter1" ref="N105F3" type="table"/><cms:entry id="N105FA" part="chapter1" ref="N105FA" type="pagenumber">8</cms:entry><cms:entry id="N109B8" part="chapter1" ref="N109B8" type="section">1.7</cms:entry><cms:entry id="N109BC" part="chapter1" ref="N109BC" type="pagenumber">9</cms:entry><cms:entry id="N109D9" part="chapter1" ref="N109D9" type="subsection">1.7.1</cms:entry><cms:entry id="N109E5" part="chapter1" ref="N109E5" type="pagenumber">10</cms:entry><cms:entry id="N10A18" part="chapter1" ref="N10A18" type="pagenumber">11</cms:entry><cms:entry id="chapter2" part="chapter2" ref="chapter2" type="chapter">2.</cms:entry><cms:entry id="N10A5A" part="chapter2" ref="N10A5A" type="pagenumber">12</cms:entry><cms:entry id="N10A87" part="chapter2" ref="N10A87" type="pagenumber">13</cms:entry><cms:entry id="chapter3" part="chapter3" ref="chapter3" type="chapter">3.</cms:entry><cms:entry id="N10AA0" part="chapter3" ref="N10AA0" type="pagenumber">14</cms:entry><cms:entry id="N10AA5" part="chapter3" ref="N10AA5" type="section">3.1</cms:entry><cms:entry id="N10AAE" part="chapter3" ref="N10AAE" type="section">3.2</cms:entry><cms:entry id="N10AB7" part="chapter3" ref="N10AB7" type="section">3.3</cms:entry><cms:entry id="N10AC1" part="chapter3" ref="N10AC1" type="pagenumber">15</cms:entry><cms:entry id="N10AC7" part="chapter3" ref="N10AC7" type="section">3.4</cms:entry><cms:entry id="N10AF7" part="chapter3" ref="N10AF7" type="pagenumber">16</cms:entry><cms:entry id="N10B0A" part="chapter3" ref="N10B0A" type="section">3.5</cms:entry><cms:entry id="N10B17" part="chapter3" ref="N10B17" type="pagenumber">17</cms:entry><cms:entry id="N10B1F" part="chapter3" ref="N10B1F" type="section">3.6</cms:entry><cms:entry id="N10B29" part="chapter3" ref="N10B29" type="table"/><cms:entry id="N10C40" part="chapter3" ref="N10C40" type="section">3.7</cms:entry><cms:entry id="N10C44" part="chapter3" ref="N10C44" type="pagenumber">18</cms:entry><cms:entry id="N10C55" part="chapter3" ref="N10C55" type="subsection">3.7.1</cms:entry><cms:entry id="N10C65" part="chapter3" ref="N10C65" type="pagenumber">19</cms:entry><cms:entry id="N10C69" part="chapter3" ref="N10C69" type="mm">624#226</cms:entry><cms:entry id="N10C75" part="chapter3" ref="N10C75" type="subsection">3.7.2</cms:entry><cms:entry id="N10CA8" part="chapter3" ref="N10CA8" type="pagenumber">20</cms:entry><cms:entry id="N10CEC" part="chapter3" ref="N10CEC" type="section">3.8</cms:entry><cms:entry id="N10CF5" part="chapter3" ref="N10CF5" type="section">3.9</cms:entry><cms:entry id="N10CF9" part="chapter3" ref="N10CF9" type="pagenumber">21</cms:entry><cms:entry id="N10D00" part="chapter3" ref="N10D00" type="table"/><cms:entry id="N10FA6" part="chapter3" ref="N10FA6" type="pagenumber">22</cms:entry><cms:entry id="chapter4" part="chapter4" ref="chapter4" type="chapter">4.</cms:entry><cms:entry id="N110A7" part="chapter4" ref="N110A7" type="pagenumber">23</cms:entry><cms:entry id="N110B1" part="chapter4" ref="N110B1" type="section">4.1</cms:entry><cms:entry id="N110BB" part="chapter4" ref="N110BB" type="table"/><cms:entry id="N110C2" part="chapter4" ref="N110C2" type="pagenumber">24</cms:entry><cms:entry id="N1131C" part="chapter4" ref="N1131C" type="section">4.2</cms:entry><cms:entry id="N11320" part="chapter4" ref="N11320" type="pagenumber">25</cms:entry><cms:entry id="N1132A" part="chapter4" ref="N1132A" type="table"/><cms:entry id="N11495" part="chapter4" ref="N11495" type="section">4.3</cms:entry><cms:entry id="N1149F" part="chapter4" ref="N1149F" type="table"/><cms:entry id="N114A6" part="chapter4" ref="N114A6" type="pagenumber">26</cms:entry><cms:entry id="N11882" part="chapter4" ref="N11882" type="table"/><cms:entry id="N11889" part="chapter4" ref="N11889" type="pagenumber">27</cms:entry><cms:entry id="N11C3A" part="chapter4" ref="N11C3A" type="section">4.4</cms:entry><cms:entry id="N11C3E" part="chapter4" ref="N11C3E" type="pagenumber">28</cms:entry><cms:entry id="N11C48" part="chapter4" ref="N11C48" type="table"/><cms:entry id="N11E31" part="chapter4" ref="N11E31" type="section">4.5</cms:entry><cms:entry id="N11E38" part="chapter4" ref="N11E38" type="pagenumber">29</cms:entry><cms:entry id="N11E3F" part="chapter4" ref="N11E3F" type="pagenumber">30</cms:entry><cms:entry id="N11E43" part="chapter4" ref="N11E43" type="mm">623#416</cms:entry><cms:entry id="N11E50" part="chapter4" ref="N11E50" type="mm">624#221</cms:entry><cms:entry id="N11E5C" part="chapter4" ref="N11E5C" type="section">4.6</cms:entry><cms:entry id="N11E60" part="chapter4" ref="N11E60" type="pagenumber">31</cms:entry><cms:entry id="N11E6A" part="chapter4" ref="N11E6A" type="table"/><cms:entry id="N1205F" part="chapter4" ref="N1205F" type="section">4.7</cms:entry><cms:entry id="N12063" part="chapter4" ref="N12063" type="pagenumber">32</cms:entry><cms:entry id="N1206C" part="chapter4" ref="N1206C" type="section">4.8</cms:entry><cms:entry id="N1207A" part="chapter4" ref="N1207A" type="table"/><cms:entry id="N12081" part="chapter4" ref="N12081" type="pagenumber">33</cms:entry><cms:entry id="N123A1" part="chapter4" ref="N123A1" type="section">4.9</cms:entry><cms:entry id="N123A5" part="chapter4" ref="N123A5" type="pagenumber">34</cms:entry><cms:entry id="N123AF" part="chapter4" ref="N123AF" type="table"/><cms:entry id="N123B6" part="chapter4" ref="N123B6" type="pagenumber">35</cms:entry><cms:entry id="N1261E" part="chapter4" ref="N1261E" type="section">4.10</cms:entry><cms:entry id="N12625" part="chapter4" ref="N12625" type="pagenumber">36</cms:entry><cms:entry id="N1262C" part="chapter4" ref="N1262C" type="table"/><cms:entry id="chapter5" part="chapter5" ref="chapter5" type="chapter">5.</cms:entry><cms:entry id="N12813" part="chapter5" ref="N12813" type="pagenumber">37</cms:entry><cms:entry id="N12827" part="chapter5" ref="N12827" type="section">5.1</cms:entry><cms:entry id="N12830" part="chapter5" ref="N12830" type="pagenumber">38</cms:entry><cms:entry id="N12846" part="chapter5" ref="N12846" type="section">5.2</cms:entry><cms:entry id="N1284A" part="chapter5" ref="N1284A" type="pagenumber">39</cms:entry><cms:entry id="N12860" part="chapter5" ref="N12860" type="pagenumber">40</cms:entry><cms:entry id="N12871" part="chapter5" ref="N12871" type="section">5.3</cms:entry><cms:entry id="N12875" part="chapter5" ref="N12875" type="pagenumber">41</cms:entry><cms:entry id="N12889" part="chapter5" ref="N12889" type="pagenumber">42</cms:entry><cms:entry id="N128AB" part="chapter5" ref="N128AB" type="section">5.4</cms:entry><cms:entry id="N128AF" part="chapter5" ref="N128AF" type="pagenumber">43</cms:entry><cms:entry id="N128BF" part="chapter5" ref="N128BF" type="section">5.5</cms:entry><cms:entry id="N128C9" part="chapter5" ref="N128C9" type="pagenumber">44</cms:entry><cms:entry id="N128CF" part="chapter5" ref="N128CF" type="section">5.6</cms:entry><cms:entry id="N128DD" part="chapter5" ref="N128DD" type="section">5.7</cms:entry><cms:entry id="N128E4" part="chapter5" ref="N128E4" type="pagenumber">45</cms:entry><cms:entry ref="chapter6" type="chapter">6.</cms:entry><cms:entry ref="N128F2" type="pagenumber">46</cms:entry><cms:entry ref="N12900" type="back"/><cms:entry id="N12902" part="N12902" ref="N12902" type="bibliography">
				7. Literaturverzeichnis</cms:entry><cms:entry id="N12906" part="N12902" ref="N12906" type="pagenumber">VIII</cms:entry><cms:entry id="N12A6D" part="N12902" ref="N12A6D" type="pagenumber">IX</cms:entry><cms:entry id="N12BCA" part="N12902" ref="N12BCA" type="pagenumber">X</cms:entry><cms:entry id="N12D0D" part="N12902" ref="N12D0D" type="pagenumber">XI</cms:entry><cms:entry id="N12E4D" part="N12902" ref="N12E4D" type="pagenumber">XII</cms:entry><cms:entry id="N12F76" part="N12902" ref="N12F76" type="pagenumber">XIII</cms:entry><cms:entry id="N13099" part="N12902" ref="N13099" type="pagenumber">XIV</cms:entry><cms:entry id="N1319F" part="N1319F" ref="N1319F" type="appendix">
				8. Publikation</cms:entry><cms:entry id="N131A1" part="N1319F" ref="N131A1" type="head"/><cms:entry id="N131A3" part="N1319F" ref="N131A3" type="pagenumber">XV</cms:entry><cms:entry id="N131A8" part="N1319F" ref="N131A8" type="p"/><cms:entry id="N131AC" part="N131AC" ref="N131AC" type="declaration">
				9. Eidesstattliche Erklärung</cms:entry><cms:entry id="N131B0" part="N131AC" ref="N131B0" type="pagenumber">XVI</cms:entry><cms:entry id="N131BF" part="N131BF" ref="N131BF" type="acknowledgement">
				10. Danksagung</cms:entry><cms:entry id="N131C3" part="N131BF" ref="N131C3" type="pagenumber">XVII</cms:entry><cms:entry part="chapter6" type=":current"/><cms:entry type=":lang">de</cms:entry><cms:entry id=":contents" part="front" ref=":contents" type=":contents">Inhaltsverzeichnis</cms:entry><cms:entry type=":help"><url href="http://...">Hilfe</url></cms:entry></cms:meta><cms:content><chapter id="chapter6" label="6.">
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				<pagenumber id="N128F2" label="46" numbering="arabic" start="46"/>Zusammenfassung</head>
			<p>Für die Melanomdiagnostik werden häufig die Antikörper HMB-45 und anti-S100 als immunhistochemische Routinemarker verwendet, obwohl HMB-45 nur eine Sensitivität von 67 - 93% hat und anti-S100 nicht spezifisch für das Melanom ist. Der monoklonale Antikörper SM5-1 wurde in Vorarbeiten mittels eines subtraktiven Immunisierungsprotokolls (Kooperationspartner Prof. YJ. Guo, Cleveland, USA) von einer humanen Melanom-Zell-Linie gewonnen. In der vorliegenden Arbeit wurde an unterschiedlichen nicht-melanozytären benignen Geweben, 16 Nävi, 84 nicht-melanozytären Tumoren sowie 745 Melanomproben das Färbeverhalten von SM5-1mittels Immunhistochemie an Paraffinschnitten charakterisiert. SM5-1 wurde zunächst mit HMB-45 und anti-S100 an 250 primären und 151 metastasierten Melanomen und in einer zweiten Stichprobe mit Antikörpern gegen Melan-A/MART-1 (A103) und Tyrosinase (T311) an 101 primären und 243 metastasierten Melanomen verglichen.<br/>Es zeigte sich, dass SM5-1 für normale Zellen der Haut und die meisten anderen normalen Zellen negativ ist. SM5-1, anti-S100 und HMB-45 färbten 100% der Nävi und 97 - 99% der 250 untersuchten primären Melanome. Während SM5-1 und anti-S100 96% der 151 Melanommetastasen korrekt identifizierten, waren für HMB-45 nur 83% der Proben positiv. Alle für HMB-45 negativen Metastasen reagierten mit SM5-1. Weder SM5-1 noch HMB-45 färbten nicht-melanozytäre Tumore, wohingegen der unspezifischere Antikörper anti-S100 21 von 84 dieser Tumore färbte. Insgesamt wurde beim primären und metastasierten Melanom für SM5-1 eine Sensitivität von 98%, für HMB-45 von 93% und für anti-S100 von 97% beobachtet. Im Vergleich der Antikörper SM5-1, A103 und T311 färbten SM5-1 92,4%, A103 82,9% und T311 71,2% der insgesamt 344primären und metastasierten Melanome. SM5-1 zeigte innerhalb einer Tumorzellpopulation ein homogeneres Färbeverhalten und eine höhere Färbeintensität bei den 243 Melanommetastasen als A103 und T311. Die Färbeintensität der 101 Primärtumore war bei allen drei Antikörpern etwa gleich.<br/>Der monoklonale Antikörper SM5-1 zeigte gegenüber den gebräuchlichen Antikörpern erhebliche Vorteile bei der immunhistochemischen Beurteilung des Melanoms, insbesondere bei dessen Metastasen. Somit kann er als Marker der ersten Wahl bei der immunhistochemischen Diagnostik von Melanomen empfohlen werden. Um die Rolle des durch SM5-1 erkannten Antigens am Krankheitsgeschehen des Melanoms zu verstehen, sind jedoch noch weitere Untersuchungen notwendig.</p>
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