Morphological Features and Prognostic Significance of ARID1A-Deficient Esophageal Adenocarcinomas

Context.-The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. Objective.-To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. Design.-One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus-associated dysplasia, when feasible. Associations between categorical clinicopathologic variables were analyzed by Fisher exact test, and survival analysis was performed by a Cox proportional hazards analysis. Results.-The study group included 97 men and 23 women (mean age, 66 years). Loss of ARID1A expression was seen in 12 of 120 EACs (10%). ARID1A-deficient tumors showed a strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had at least one feature reminiscent of high microsatellite instability colon carcinomas (mucinous or medullary differentiation, marked intratumoral or peritumoral lymphoid infiltrate). A mutant p53 pattern was present in 52 of 120 EACs (43%) and showed no correlation with ARID1A deficiency (P > 05). MLH1 loss was present in only 2 of 120 EACs (2%); both of which were also deficient in ARID1A. ARID1A-deficient EACs showed a trend toward increased risk of nodal metastasis but had no effect on overall patient survival. Conclusions.-ARID1A-deficient EACs show a phenotype similar to colon cancer with high microsatellite instability but do not appear to have any prognostic significance. Concurrent MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may be a primary driver of carcinogenesis in a subset of EACs.