Microsatellite instability and somatic mutations in endometrial carcinomas

Recently, microsatellite instability (MI) has been demonstrated in some types of human cancers. In this study, we attempted to determine the frequency of MI in endometrial cancers and evaluate whether replication error (RER)-positive phenotype is correlated with known genetic mutations or the aberrations of other pathways in endometrial cancers. Seventy-two primary endometrial cancers were examined for microsatellite instability. Eleven tumors (15%) had RERs at two or more microsatellite loci, suggesting that generalized MI may be a molecular manifestation of endometrial cancers. We next examined whether the MI was associated with changes in the K-ras protooncogene, p53 tumor suppressor gene, and 18q LOH, which were frequently detected in endometrial cancers. The MI did not confer the potential to produce point mutations in the K-ras gene or 18q LOH, whereas the data were insufficient to identify the correlation between MI and p53 mutations in the cancers. These results suggest the presence of multiple mutation subsets that act in a complementary fashion in endometrial cancer development.