Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability.

AIM To investigate the role of DNA microsatellite instability (MSI) in gastric carcinogenesis by studying associations between MSI status, clinicopathological features, and loss of genetic loci. METHODS Six microsatellite loci and loss of heterozygosity at APC, DCC, and MCC were analysed by polymerase chain reaction based methods in 53 cases of advanced gastric cancer. RESULTS MSI was observed in 32.1% of gastric carcinomas (17/53) and 20% of foci of intestinal metaplasia (3/15). Seven gastric carcinomas (13.7%) were MSI-high (MSI-H) (three loci or more) and 10 (18.9%) were MSI-low (MSI-L) (one or two loci). The frequency of MSI-H was higher in intestinal (25.0%) than in diffuse carcinomas (3.7%) (p < 0.05). None of the MSI-H tumours showed loss of heterozygosity at APC, MCC, or DCC loci. CONCLUSIONS MSI may have an important and early role in a subset of gastric cancers, particularly the intestinal type. The MSI-H subset of gastric cancer has features in common with its colorectal counterpart, whereas MSI-L and microsatellite stable cancers appear to develop through the loss of heterozygosity pathway.