Die Expression von c-erbB-2 und Topoisomerase IIα in Relation zur Zytostatikaresistenz beim Ovarialkarzinom

Zusammenfassung

In der vorliegenden Studie untersuchten wir die Rolle des c-erbB-2 für die Zytostatikaresistenz beim Ovarialkarzinom. Die Überexpression von c-erbB-2 mRNA im Tumorgewebe war mit einem kürzeren Überleben von Patientinnen mit primärem Ovarialkarzinom verbunden (p = 0,0001, n = 77) und ein unabhängiger prognostischer Faktor im Proportional Hazard Modell (p = 0,035). Eine signifikante Assoziation bestand zwischen der Expression von c-erbB-2 mRNA und Überleben in der Subgruppe der Patientinnen, die eine Standardchemotherapie mit Cisplatin/Carboplatin und Cyclophosphamid erhalten hatten (p = 0,0003). Darüber hinaus verbesserte die Applikation einer Standardchemotherapie das Überleben in der Subgruppe der Patientinnen mit geringer Expression von c-erbB-2 mRNA (p = 0,013), aber nicht in der Subgruppe der Patientinnen mit hoher Expression von c-erbB-2 mRNA (p = 0,359). Die Expression der c-erbB-2 mRNA korrelierte mit der Expression der mRNA von Topoisomerase IIα (p = 0,009), aber nicht mit der Expression der mRNA von Topoisomerase IIβ (p = 0,221). Die Bestimmungen erfolgten durch eine reverse semiquantitative PCR-Technik. Die Daten stützen die Hypothese, dass Topoisomerase IIα, das mit der Expression von c-erbB-2 korreliert, an der Entwicklung der Resistenz c-erbB-2-exprimierender Tumoren beteiligt ist.

Abstract

In the present study, we examined die role of c-erbB-2 for chemoresistance in ovarian cancer. Overexpression of c-erbB-2 mRNA in tumor tissue was associated with a shorter survival of patients with primary ovarian cancer (P = 0.0001, N = 77) and was an independent prognostic factor in the proportional-hazard model (P = 0.035). A significant association between expression of c-erbB-2 mRNA und survival was obtained for the subgroup of patients who received a standard chemotherapy with carboplatin or cisplatin and cyclophosphamide (P = 0.0003). In addition, the application of a standard chemotherapy improved the survival of patients with relatively low c-erbB-2 expression (P = 0.013), but not of patients with overexpression of c-erbB-2 (P = 0.359). Expression of c-erbB-2 mRNA correlated with expression of topoisomerase IIα mRNA determined by a reverse semiquantitative PCR technique (P = 0.009), whereas expression of c-erbB-2 und topoisomerase IIβ mRNA dit not correlate (P = 0.221). The data suggest that topoisomerase IIα, which correlates with c-erbB-2 expression, contributes to the resistance of c-erbB-2-overexpressing carcinomas.

c-erbB-2 - Topoisomerase IIα - Ovarialkarzinom - Zytostatikaresistenz

c-erbB-2 - Topoisomerase IIα - Chemoresistance - Ovarian cancer

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