Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8+ TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- Abstract:
- 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
- Authors:
- K Heinze, TM Nazeran, S Lee, P Krämer, ES Cairns, DS Chiu, SC Leung, EY Kang, NS Meagher, CJ Kennedy, J Boros, F Kommoss, H-W Vollert, F Heitz, A du Bois, P Harter, M Grube, B Kraemer, A Staebler, FK Kommoss, S Heublein, H-P Sinn, N Singh, A Laslavic, E Elishaev, A Olawaiye, K Moysich, F Modugno, R Sharma, AH Brand, PR Harnett, A DeFazio, RT Fortner, J Lubinski, M Lener, A Tołoczko-Grabarek, C Cybulski, H Gronwald, J Gronwald, P Coulson, MA El-Bahrawy, ME Jones, MJ Schoemaker, AJ Swerdlow, KL Gorringe, I Campbell, L Cook, SA Gayther, ME Carney, YB Shvetsov, BY Hernandez, LR Wilkens, MT Goodman, C Mateoiu, A Linder, K Sundfeldt, LE Kelemen, A Gentry-Maharaj, M Widschwendter, U Menon, KL Bolton, J Alsop, M Shah, M Jimenez-Linan, PD Pharoah, JD Brenton, KL Cushing-Haugen, HR Harris, JA Doherty, B Gilks, P Ghatage, DG Huntsman, GS Nelson, AV Tinker, C-H Lee, EL Goode, BH Nelson, SJ Ramus, S Kommoss, A Talhouk, M Köbel, MS Anglesio
- Journal:
- J Pathol
- Citation info:
- 256(4):388-401
- Publication date:
- 1st Apr 2022
- Full text
- DOI