Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma

Pauline Krämer, Aline Talhouk, Mary Anne Brett, Derek S Chiu, Evan S Cairns, Daniëlla A Scheunhage, Rory Fl Hammond, David Farnell, Tayyebeh Mehrane Nazeran, Marcel Grube, Zhouchunyang Xia, Janine Senz, Samuel Leung, Lukas Feil, Jana Pasternak, Katherine Dixon, Andreas Hartkopf, Bernhard Krämer, Sara Brucker, Florian HeitzAndreas du Bois, Philipp Harter, Felix Kommoss, Hans-Peter Sinn, Sabine Heublein, Friedrich Kommoss, Hans-Walter Vollert, Ranjit Manchanda, Cornelis D de Kroon, Hans W Nijman, Marco de Bruyn, Emily F Thompson, Ali Bashashati, Jessica N McAlpine, Naveena Singh, Anna V Tinker, Annette Staebler, Tjalling Bosse, Stefan Kommoss, Martin Köbel, Michael S Anglesio*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: Endometrioid ovarian carcinoma (ENOC) is generally associated with a more favorable prognosis compared to other ovarian carcinomas. Nonetheless, current patient treatment continues to follow a "one-size-fits-all" approach. Even though tumor staging offers stratification, personalized treatments remain elusive. As ENOC shares many clinical and molecular features with its endometrial counterpart, we sought to investigate TCGA-inspired endometrial cancer (EC) molecular subtyping in a cohort of ENOC.

EXPERIMENTAL DESIGN: Immunohistochemistry and mutation biomarkers were used to segregate 511 ENOC tumors into four EC-inspired molecular subtypes: low-risk POLE mutant (POLEmut); moderate-risk mismatch repair deficient (MMRd); high-risk p53 abnormal (p53abn); moderate-risk with no specific molecular profile (NSMP). Survival analysis with established clinicopathological and subtypes specific features was performed.

RESULTS: 3.5% of cases were POLEmut, 13.7% MMRd, 9.6% p53abn and 73.2% NSMP, each showing distinct outcomes (p <0.001) and survival similar to observations in EC. Median OS was 18.1 years in NSMP, 12.3 years in MMRd; 4.7 years in p53abn and not reached for POLEmut cases. Subtypes were independent of stage, grade, and residual disease in multivariable analysis.

CONCLUSIONS: EC-inspired molecular classification provides independent prognostic information in ENOC. Our findings support investigating molecular-subtype specific management recommendations for ENOC patients; for example, subtypes may provide guidance when fertility-sparing treatment is desired. Similarities between ENOC and EC suggest that ENOC patients may benefit from management strategies applied to EC and the opportunity to study those in umbrella trials.

Original languageEnglish
Pages (from-to)1503
Number of pages12
JournalClinical Cancer Research
Volume83
Issue number5
Early online date31-Jul-2020
DOIs
Publication statusPublished - Nov-2020

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