Evaluierung der Defizienz der Mismatch-Repair-Enzyme und der Expressionsmuster der Tumorsuppressorproteine p53 und p16 in der Immunhistochemie als prognostische Marker des Ovarialkarzinoms

Die vorliegende Arbeit hatte das Ziel, die MMR-Defizienz sowie den Expressionstatus der Tumorsuppressorproteine p53 und p16 beim Ovarialkarzinom als mögliche prognostische Marker in der IHC zu untersuchen. Zeigten sich bei anderen Tumorentitäten in den letzten Jahren zwar vielversprechende Einordn...

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Bibliographic Details
Main Author: Rozmyslowski, Janina Meike Kim
Contributors: Wagner, Uwe (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2021
Online Access:PDF Full Text
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The aim of this study was to investigate the role of MMR deficiency and the expression status of the tumor suppressor proteins p53 and p16 in ovarian cancer as possible prognostic markers in immunochemistry. While other tumor entities have shown promising classifications of MMR deficiency and MSI status as a prognostic markers in both positive and negative directions in recent years, this investigation shows no comparable prognostic effect of MMR deficiency or the degree of MMR-enzyme expression in the IHC on the PFS of our study cohort. This is possibly due to the low number of cases in our cohort. However, further investigations into a possible protective effect of an MMR deficiency on immunohistochemically proven MMR-deficient ovarian carcinomas, especially HGSOCs, appear worthwhile, since no recurrence could be found in 50% of the MMR-deficient cases of our cohort during the observation period. The degree of expression of the tumor suppressor protein p53 in the IHC shows no prognostic significance with regard to the PFS in this study. Given the multitude of possible mutations of TP53 and their different properties on the carcinogenesis of ovarian cancer, a lack of significance as a prognostic marker in the IHC is not surprising. Even an optimized evaluation of p53 in IHC without additional molecular genetic testing, leaves it unclear to a certain extent which mutation hides behind the immunohistochemical appearance. In the absence of therapeutic consequences up to now, the importance of p53 in IHC is more likely to be seen as a diagnostic criterion for HGSOC. The same applies to the combined evaluation of p53 and p16 in serous ovarian cancer, even if a correlation with the assigned histological grading could not be clearly shown due to the overrepresentation of the HGSOC in our cohort. The expression status of p16 in this study also did not show any prognostic significance with regard to the PFS, which is consistent with observations already made on HGSOC, which is disproportionately represented in our cohort. The role of the p16 expression status therefore remains limited to the diagnostic function.