Lowenthal BM, Nason KS, Pennathur A, et al. - Tissue microarrays representing 316 surgically resected esophageal adenocarcinomas without neoadjuvant treatment were assessed for ARID1A and mismatch repair (MMR) proteins via immunohistochemistry in order to determine whether that ARID1A loss was related to prognosis and DNA MMR protein deficiency in esophageal adenocarcinoma. In 41 of 316 adenocarcinomas, loss of ARID1A expression (ARID1A-loss) was discovered. In 5%, MMR deficiency was recognized, however, it was discovered more often in ARID1A-loss adenocarcinomas vs ARID1A-retained adenocarcinomas. Morphologically, ARID1A-loss adenocarcinomas commonly showed peritumoral lymphoid aggregates and tumor infiltrating lymphocytes. In individuals with locally advanced or metastatic disease (stages III or IV, n = 169), people with ARID1A-loss adenocarcinomas (n = 22) had longer overall survival compared with individuals with ARID1A-retained adenocarcinomas. In these individuals, ARID1A-loss corelated to a 56% decrease in mortality irrespective of other prognostic factors. In conclusion, loss of ARID1A expression is related to deficiency of DNA MMR protein in esophageal adenocarcinoma. Moreover, for individuals with locally advanced or metastatic esophageal adenocarcinomas, ARID1A loss is independently correlated with a more favorable prognosis.