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ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1623 endometriosis-associated ovarian carcinomas, including 1078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas, through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8 + tumour-infiltrating lymphocytes (CD8 + TILs), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOCs and 25% of ENOCs. We found no associations between ARID1A loss and outcomes, stage, age, or CD8 + TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p = 0.012) and was associated with MMRd (p < 0.001) and the presence of CD8 + TILs (p = 0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOCs we also observed an association with ARID1A loss-of-function mutation as a result of small indels (p = 0.035, versus single nucleotide variants). In ENOC, the association with ARID1A loss, CD8 + TILs, and age appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8 + TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. © 2021 The Pathological Society of Great Britain and Ireland., (© 2021 The Pathological Society of Great Britain and Ireland.)

Objective: To assess ARID1A-encoded protein (BAF250a) and phosphorylated AKT (pAKT) expression, apoptosis, and the DNA damage response pathway in endometrioid and clear cell ovarian cancers (endometriosis-associated ovarian cancers [EAOCs]), and benign endometriotic ovarian cysts., Methods: In a retrospective study, tissue samples were reviewed from patients who had undergone surgery for EAOC or endometriotic ovarian cysts at a center in Montreal, QC, Canada, between 2000 and 2012. A tissue microarray including cases of endometrioid carcinoma, clear cell carcinoma, contiguous endometriosis (i.e. apparently benign endometriosis near the EAOC), and benign endometriotic ovarian cysts, was analyzed for the expression of various proteins., Results: Loss of BAF250a expression was seen in 13 (22%) of 59 endometrioid cancers, 17 (47%) of 36 clear cell cases, 8 (44%) of 18 contiguous endometriosis cases, and 3 (8%) of 66 benign endometriotic ovarian cysts. In tissues showing loss of BAF250a, expression of pAKT, γH2AX, BIM, and BAX was higher in EAOC and contiguous endometriosis than in benign endometriosis (P<0.05), whereas expression of pATM, pCHK2, and Bcl2 was low. All proteins except for Bcl2 showed low expression in benign endometriosis., Conclusion: Loss of ARID1A-encoded protein seems to be an early event in EOAC, along with pAKT activation, alteration of γH2AX, and concomitant activation of the apoptosis pathway., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)