ARID1A expression in gastric adenocarcinoma: clinicopathological significance and correlation with DNA mismatch repair status

AIM: To analyze the mismatch repair (MMR) status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas. METHODS: We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas. The results were further correlated with clinicopathological variables. RESULTS: The loss of any MMR protein expression, indicative of MMR deficiency, was observed in 38 cases (7.8%) and was significantly associated with an older age (68.6±9.2 vs 60.4±11.7, P<0.001), a female sex (55.3% vs 31.3%, P=0.004), an antral location (44.7% vs 25.7%, P=0.021), and a differentiated histology (57.9% vs 39.7%, P=0.023). Abnormal ARID1A expression, including reduced or loss of ARID1A expression, was observed in 109 cases (22.3%) and was significantly correlated with lymphatic invasion (80.7% vs 69.5%, P=0.022) and lymph node metastasis (83.5% vs 73.7%, P=0.042). The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency (47.4% vs 20.2%, P<0.001). A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor (HR=1.36, 95%CI: 1.01-1.84; P=0.040). CONCLUSION: Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion, lymph node metastasis, poor prognosis, and MMR deficiency in gastric adenocarcinomas.