Dokument: Untersuchung möglicher immunologischer Zielstrukturen für eine adjuvante Therapie des operablen Plattenepithelkarzinoms des Ösophagus

Titel:

Untersuchung möglicher immunologischer Zielstrukturen für eine adjuvante Therapie des operablen Plattenepithelkarzinoms des Ösophagus

URL für Lesezeichen:

https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=7933

URN (NBN):

urn:nbn:de:hbz:061-20080527-131300-7

Kollektion:

Dissertationen

Sprache:

Deutsch

Dokumententyp:

Wissenschaftliche Abschlussarbeiten » Dissertation

Medientyp:

Text

Autor:

Siegmund, Annika [Autor]

Dateien:

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Dateien vom 27.05.2008 / geändert 27.05.2008

Beitragende:

Prof. Dr. Knoefel, W. [Gutachter]
Prof. Dr. Poremba, Christopher [Gutachter]

Stichwörter:

Ösophaguskarzinom, Ep-CAM, HER-2/neu, adjuvante Therapie

Dewey Dezimal-Klassifikation:

600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit

Beschreibung:

Einleitung: Ösophaguskarzinome haben generell eine schlechte Prognose und der Nutzen der derzeitig verfügbaren adjuvanten Therapien wird nach wie vor kontrovers diskutiert. Aufgabe dieser Arbeit war die Expressionsanalyse zweier möglicher immunologischer Zielstrukturen für eine adjuvante Therapie des operablen Plattenepithelkarzinoms des Ösophagus.
Material und Methoden: Mit immunhistochemischen Methoden wurde die Expression von Ep-CAM und p185HER-2 an 70 Plattenepithelkarzinomen des Ösophagus untersucht. Für 53 Patienten waren klinische FollowUp-Daten vorhanden, mit denen die Studienergebnisse statistisch korreliert werden sollten.
Ergebnisse: Ep-CAM wird von der Mehrzahl der Karzinome exprimiert, wobei eine generelle Neo-Expression nicht mit den klinisch-pathologischen Parametern korrelierte. Die in 41% der Fälle nachgewiesene starke Expression erwies sich jedoch als unabhängiger prognostischer Faktor sowohl für das rezidivfreie als auch für das Gesamtüberleben. Ep-CAM-exprimierende Tumoren scheinen sich also durch ein aggressiveres biologisches Verhalten auszuzeichnen. p185HER-2 wurde von 16% der untersuchten Tumoren exprimiert, davon nur in 4% der Fälle stark. Eine Korrelation mit klinischen Parametern und Prognose war nicht zu beobachten. Mittels Chromogener In-Situ-Hybridisierung konnte gezeigt werden, daß die starke Überexpression in erster Linie auf eine HER-2-Genamplifikation zurückzuführen ist. Dieser Mechanismus war für das Ösophaguskarzinom zuvor noch nicht beschrieben worden. Im untersuchten Kollektiv fand sich eine Subgruppe Ep-CAM-p185HER-2- koexprimierender Tumoren, die durch ein signifikant kürzeres Gesamtüberleben gekennnzeichnet war.
Schlußfolgerung: Mit der Expressionsanalyse ist eine Risikostratifizierung der Karzinome denkbar. Zusätzlich wurde die Identifizierung potentieller Kandidaten für eine adjuvante Immuntherapie (als Monotherapie mit einem anti-Ep-CAM-Antikörper oder in Kombination mit dem anti-p185HER-2-Antikörper Trastuzumab) ermöglicht.

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Lizenz:

Urheberrechtsschutz

Bezug:

10/2001 - 05/2008; Beginn in der Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie des Universitätsklinikums Hamburg-Eppendorf; Fortsetzung in der Klinik für Allgemein-, Viszeral- und Kinderchirurgie der Heinrich-Heine-Universität Düsseldorf

Fachbereich / Einrichtung:

Medizinische Fakultät

Dokument erstellt am:

27.05.2008

Dateien geändert am:

27.05.2008

Promotionsantrag am:

25.09.2007

Datum der Promotion:

08.05.2008