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Prognostic and Immunological Significance of ARID1A Status in Endometriosis-Associated Ovarian Carcinoma

Abstract:
ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumor 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+ tumor-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. 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 associated with MMRd (p
Authors:
K Heinze, T Nazeran, S Lee, P Krämer, E Cairns, D Chiu, SCY Leung, EY Kang, N Meagher, C Kennedy, J Boros, F Kommoss, H-W Vollert, F Heitze, A du Bois, P Harter, M Grube, B Kraemer, A Staebler, FKF Kommoss, S Heublein, H-P Sinn, N Singh, A Laslavic, E Elishaev, A Olawaiye, K Moysich, F Modugno, R Sharma, A Brand, P Harnett, A DeFazio, R Fortner, J Lubinski, M Lener, A Tołoczko-Grabarek, C Cybulski, H Gronwald, J Gronwald, P Coulson, M El-Bahrawy, M Jones, M Schoemaker, A Swerdlow, K Gorringe, I Campbell, L Cook, S Gayther, M Carney, Y Shvetsov, B Hernandez, L Wilkens, M Goodman, C Mateoiu, A Linder, K Sundfeldt, L Kelemen, A Gentry-Maharaj, M Widschwendter, U Menon, K Bolton, J Alsop, M Shah, M Jimenez-Linan, PDP Pharoah, J Brenton, K Cushing-Haugen, H Harris, J Doherty, B Gilks, P Ghatage, D Huntsman, G Nelson, A Tinker, C-H Lee, E Goode, B Nelson, S Ramus, S Kommoss, A Talhouk, M Köbel, M Anglesio
Publication date:
1st Aug 2021
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