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

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.