Expression of hMLH1 is inactivated in the gastric adenomas with enhanced microsatellite instability

Microsatellite instability (MSI) and frameshift mutations in the genes cont aining coding nucleotide repeats have been reported in a subset of gastric adenomas, however the inactivation profiles of DNA mismatch repair genes in MSI-positive gastric adenomas have not been characterized. To address the origin of MSI in gastric adenomas, expressions of hMLH1 and hMSH2 were expl ored in 86 gastric adenomas. Gastric carcinomas, of which 16 were MSI-posit ive and 22 MSI-negative, were used as controls. MSI was found in 15 (17%) o f gastric adenomas. Absent or decreased hMLH1 expression by immunohistochem istry was noted in most of the MSI-positive adenomas (13/15, 87%) and carci nomas (14/16, 88%), and all of these tumours showed methylation of the hMLH 1 gene promoter. In contrast, rare inactivation of hMLH1 expression was fou nd in MSI-negative adenomas (3/71, 4%) and carcinomas (2/22, 9%). Intense e xpression of hMSH2 gene product was observed in most of the gastric adenoma s and carcinomas regardless of MSI status. These findings indicate that the inactivation of hMLH1 gene expression by promoter methylation is an early event and might be the origin of MSI-positive gastric adenomas. (C) 2001 Ca ncer Research Campaign.