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10780432ccr201268-sup-240661_2_supp_6412788_qd690j.pdf (6.73 MB)

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

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journal contribution
posted on 2023-03-31, 22:05 authored by Pauline Krämer, Aline Talhouk, Mary Anne Brett, Derek S. Chiu, Evan S. Cairns, Daniëlla A. Scheunhage, Rory F.L. Hammond, David Farnell, Tayyebeh M. Nazeran, Marcel Grube, Zhouchunyang Xia, Janine Senz, Samuel Leung, Lukas Feil, Jana Pasternak, Katherine Dixon, Andreas Hartkopf, Bernhard Krämer, Sara Brucker, Florian Heitz, Andreas du Bois, Philipp Harter, Felix K.F. 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

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Funding

Canadian Ovarian Cancer Research Consortium's COEUR

Terry Fox Research Institute

Centre hospitalier de l'Université de Montréal

Terry Fox Research Institute's pan-Canadian Ovarian Cancer study

BC Cancer Foundation

History

ARTICLE ABSTRACT

Endometrioid ovarian carcinoma (ENOC) is generally associated with a more favorable prognosis compared with 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 The Cancer Genome Atlas–inspired endometrial carcinoma (EC) molecular subtyping in a cohort of ENOC. IHC 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), and moderate-risk with no specific molecular profile (NSMP). Survival analysis with established clinicopathologic and subtype-specific features was performed. A total of 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 multivariate analysis. EC-inspired molecular classification provides independent prognostic information in ENOC. Our findings support investigating molecular subtype–specific management recommendations for patients with ENOC; for example, subtypes may provide guidance when fertility-sparing treatment is desired. Similarities between ENOC and EC suggest that patients with ENOC may benefit from management strategies applied to EC and the opportunity to study those in umbrella trials.

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    Clinical Cancer Research

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    Keywords

    BiomarkersGynecological CancersEndometrial cancerOvarian cancerTumor Staging

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    CC BY

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