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

AimTo analyze the mismatch repair (MMR) status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.MethodsWe examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas. The results were further correlated with clinicopathological variables.ResultsThe 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).ConclusionOur observations suggest that the AIRD1A inactivation is associated with lymphatic invasion, lymph node metastasis, poor prognosis, and MMR deficiency in gastric adenocarcinomas.