Microsatellite instability is linked to loss of hMLH1 expression in advanced gastric cancers: Lack of a relationship with the histological type and phenotype

Background. It has been suggested that the prevalence of microsatellite instability (MSI) is high in intramucosal differentiated gastric cancers with gastric foveolar phenotypic expression, and that these tumors are prone to lose their glandular structures and progress to undifferentiated-type lesions. To test this hypothesis, we examined the relationships among human MutL homologue 1 (hMLH1) expression (which is linked to MSI), the phenotype, and the histological type in patients with advanced and intramucosal gastric cancer. Methods. We analyzed hMLH1 expression by immunohistochemistry in 70 advanced and 30 intramucosal gastric cancers with histological evaluation and assessment of the phenotype, and Cdx2 expression determined by immunohistochemistry. The MSI status was also examined in 20 cases. Results. Thirteen (18.6%) advanced and 5 (16.7%) intramucosal gastric cancers were judged to be hMLH1-negative. In the advanced cases, no association was observed between the histological type and the phenotype and loss of hMLH1. In the intramucosal cases, MUC5AC expression was observed in all 5 hMLH1-negative differentiated-type cancers. However, no hMLH1-negative lesions were detected in the intramucosal undifferentiated cancers (0/14; P < 0.05 vs differentiated types). In the advanced cases, MSI-positivity (MSI +) and loss of hMLH1 expression did correlate (P < 0.0001), while no association was observed between MSI +, histological type, and phenotype. Conclusion. Our data support the hypothesis that, phenotypically, some MSI-positive differentiated gastric cancers of gastric foveolar phenotypic expression may easily change, from gastric to intestinal phenotypic expression, also changing, histologically, from differentiated to undifferentiated type with progression.