2022-RA-1479-ESGO Sex hormone receptor expression, MSH2 and MSH6 loss, but not β-catenin nuclear translocation, is concordant between synchronous endometrial and ovarian carcinomas

Introduction/Background Synchronous endometrial and ovarian carcinoma (SEOC) accounts for 10% of 5% cancers. SEOC tumours are staged separately but most demonstrate clonality. The ProMisE algorithm classifies carcinomas into p53 aberrant, mismatch repair deficient (MMRd), POLE mutant no specific molecular profile, up to ½ which CTNNB1 (CTNNB1mut). Methodology Formalin-fixed paraffin-embedded (FFPE) tissue was obtained from 34 patients with haematoxylin eosin (H&E) review, immunohistochemistry (IHC). Progesterone receptor (PR) estrogen (ER) expression scored between 0–300. Tumours were assessed MMRd via MLH1, MSH2, MSH6 PMS2 staining, presence nuclear β-catenin (a surrogate marker CTNNB1mut). Results endometrioid (55/68, 80.9%), clear cell (4/68, 5.9%) mixed endometrioid/clear (9/68, 13.2%) histology, almost all wildtype (67/68). Neither ER (p = 0.15) nor PR (p 0.98) statistically significantly different paired tumours. 9 cases (26.5%); 4 2 had MSH2/MSH6 loss respectively, this conserved the 16 (47.1%) exhibited staining only 6 tumour sites. Conclusion expression, MSH2 loss, not β-catenin, is concordant tumours, suggesting that function may differ carcinomas, even in synchronous context. Conserved and/or a subset suggests underlying Lynch syndrome. Whole exome sequencing underway investigate mutational landscapes including mutation status MMR genes CTNNB1.