Distinct clinical features and outcomes of gastric cancers with microsatellite instability

Microsatellite instability (MST) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MST+ gastric cancers remain unclear. To determine the correlation between MST status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MST in the BAT-26 marker. Because it has been proven that MST at BAT-26 reflects the MST+ phenotype, cancers with alteration at BAT-26 were categorized as having the MST+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MST+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MST+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P<.05). By multivariate logistic regression, MST+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P<.001). MST+ gastric cancers displayed frequent frame-shift mutations of transforming growth factor-beta; type H receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MST+ phenotype correlated with patient survival in advanced gastric carcinoma (P=.046). In conclusion, MST+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.