Molecular-based classification algorithm for endometrial carcinoma to categorize ovarian endometrioid carcinoma into prognostically significant groups.

Abstract

e17081 Background: The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR) and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma (OEC), their role in predicting its molecular profile and prognosis is still not fully explored. Methods: OECs resected in a 14 year period were retrieved. Only tumors with confirmed endometrioid histology and negative WT1 were included. POLE mutational analysis and immunohistochemistry for p53, MLH1, MSH2, MSH6 and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. Following the molecular classifier proposed for endometrial carcinoma ( B J Cancer 2015;113:299-310), cases were classified as: POLE mutated, MMR abnormal, p53 abnormal and p53 wild type. Clinicopathologic information was recorded including patient outcome. Results: 73 tumors were successfully reviewed and tested. Of these, 8 (11%) were POLE mutated, 6 (8%) were MMR abnormal and 17 (23%) were p53 abnormal; the remaining 42 cases (58%) were p53 wild type (no POLE, p53 or MMR abnormalities). Mean follow-up period was 69 months (median 62, range 1-179). The molecular classification was an independent predictor for disease free and overall survival on multivariate analysis (p = 0.005 and 0.045 respectively, Cox proportional hazard model). POLE mutated and MMR abnormal groups had 100% 5 year DFS and OS. p53 wild type cases had intermediate survival rates (86% DFS and OS). Conversely, the p53 abnormal group had worse outcomes with 42% DFS and 76% OS at 5 years. Conclusions: OEC can be classified into prognostically distinct subgroups by testing for molecular surrogates, akin to endometrial cancer. MMR and POLE alterations seem to identify a subset of ovarian endometrioid carcinomas with excellent outcome; conversely, abnormal p53 expression carries a worse prognosis. In the era of personalized medicine, the use of these markers in the routine evaluation of ovarian endometrioid tumors should be considered.