Prevalence and clinical implications of mismatch repair (MMR) deficiency in unselected non-serous epithelial ovarian cancer (EOC) patients (pts).

person Mariana Scaranti The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom info_outline Mariana Scaranti, Krithika Murali, Cecilia Orbegoso, Katherine Vroobel, Susana N. Banerjee, Martin Eric Gore, Ayoma Attygalle, Angela George

Authors person Mariana Scaranti The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom info_outline Mariana Scaranti, Krithika Murali, Cecilia Orbegoso, Katherine Vroobel, Susana N. Banerjee, Martin Eric Gore, Ayoma Attygalle, Angela George Organizations The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom, The Royal Marsden NHS Foundation Trust, London, United Kingdom Abstract Disclosures Research Funding Other Background: It has previously been reported that 6-7% of clear cell (CC) and endometrioid (E) ovarian cancers are MMR deficient (MMRd). The prevalence of MMRd in other histological subtypes and correlation with germline (g) MMR (Lynch Syndrome) mutations in unselected non-serous EOC pts is less clear. MMRd in solid tumors has been associated with enhanced response to immunotherapy, hence knowledge of MMR status has therapeutic and familial implications. We aimed to study the prevalence and implications of MMRd and gMMRd in unselected pts with non-serous EOC. Methods: Routine immunohistochemistry (IHC) was performed for the MMR proteins MLH1, MSH2, MSH6 and PMS2 in all non-serous EOC pts from June 2016; retrospective MMR IHC testing in pts in follow-up was performed. Pts with MMRd tumors were referred for gMMR testing. Results: We analyzed 66 unselected pts with non-serous EOC. Median age was 56.4 years (yrs). The majority had E ovarian cancer (54.5%) followed by CC (25.8%), mixed histology (12.1%), mucinous (4.5%) and mullerian (3%) subtypes. Endometriosis was noted in 45.5% of pts, and 75% were FIGO stage I and II at diagnosis. Seventeen pts (25.8%) had concurrent endometrial cancer, all Grade I. On IHC, 15.2% were MMRd: 5 E, 2 CC, 2 mixed and 1 mullerian-type. Of these, 3 pts (30%) had gMMR mutation, 2/3 did not meet the Revised Bethesda criteria for testing. A lower average body mass index (Kg/m 2 ) was noted in MMRd 25.9 versus 30.1 in MMR proficient (MMRp). Median age at diagnosis was 53.5 yrs in the MMRd and 57.7 yrs in MMRp. A higher frequency of concurrent endometrial cancer was observed on the MMRd group (60%) versus (20%) on MMRp (p = 0.007). No statistically significant difference in overall survival or disease-free survival was observed between the MMRd and MMRp population. Conclusions: Our study has shown a higher prevalence of somatic MMRd in non-serous EOC (15.2%) than in previously published literature with a significant proportion found to carry gMMR mutations (4.5%). These interim findings support the role of universal MMR IHC testing in non-serous EOC regardless of family history. Patterns of MMR loss IHC (n) gMMR mutation found MSH2/MSH6 2 1 MSH2 MLH1/PMS2 4 1 MLH1 MSH6 2 1 MLH1 PMS2 2 0