Endometrial cancer molecular risk stratification is equally prognostic for endometrioid ovarian carcinoma

Kramer, P.; Talhouk, A.; Brett, M.A.; Chiu, D.S.; Cairns, E.S.; Scheunhage, D.A.; Hammond, R.F.L.; Farnell, D.; Nazeran, T.M.; Grube, M.; Xia, Z.C.Y.; Senz, J.; Leung, S.; Feil, L.; Pasternak, J.; Dixon, K.; Hartkopf, A.; Kramer, B.; Brucker, S.; Heitz, F.; Bois, A. du; Harter, P.; Kommoss, F.K.F.; Sinn, H.P.; Heublein, S.; Kommoss, F.; Vollert, H.W.; Manchanda, R.; Kroon, C.D. de; Nijman, H.W.; Bruyn, M. de; Thompson, E.F.; Bashashati, A.; McAlpine, J.N.; Singh, N.; Tinker, A.V.; Staebler, A.; Bosse, T.; Kommoss, S.; Kobel, M.; Anglesio, M.S.

doi:doi:10.1158/1078-0432.CCR-20-1268

Purpose: 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.Experimental Design: 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 subtypespecific features was performed.Results: A total of 3.5% of cases were POLEmut, 13.7% MMRd, 9.6...Show morePurpose: 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.Experimental Design: 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 subtypespecific features was performed.Results: 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.Conclusions: 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.Show less

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Endometrial cancer molecular risk stratification is equally prognostic for endometrioid ovarian carcinoma