Differences in genomic instability between intestinal- and diffuse-type gastric cancer
Microsatellite alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) are observed in most (70% to 80%) gastric carcinomas. To determine whether the microsatellite genotypes are correlated with clinicopathological features, 118 patients with gastric carcinomas were examined by using polymorphic microsatellite markers for LOH on 5 gastric cancer-associated chromosome arms and non-polymorphic BAT markers for MSI. Microsatellite genotypes were categorized as high-frequency MSI (MSI-H), high-level LOH (LOH-H), low-level LOH (LOH-L) and LOH non-detectable (LOH-N). A significant fraction of the MSI-H, LOH-H and LOH-L types was observed in intestinal-type gastric carcinomas, whereas the LOH-N type was highly associated with diffuse-type tumors (p = 0.00162). There was a close relationship between microsatellite genotype and TNM (tumor-node-metastasis) stage (p = 0. 001). Univariate analysis showed that patients of LOH-H or LOH-N types and those of MSI-H or LOH-L types correlated with poor and favorable survival, respectively, not only in all tumor stages (p = 0.0001) but also in stages II and III (p = 0.0271). It is likely that the major genotypes of gastric carcinomas can be placed into at least 4 microsatellite categories, thus allowing the construction of a comprehensive genetic classification useful for the prediction of diverse clinical courses.