Recently, microsatellite instability (MI) has been demonstrated in som
e types of human cancers. In this study, we attempted to determine the
frequency of MI in endometrial cancers and evaluate whether replicati
on error (RER)-positive phenotype is correlated with known genetic mut
ations or the aberrations of other pathways in endometrial cancers. Se
venty-two primary endometrial cancers were examined for microsatellite
instability. Eleven tumors (15%) had RERs at two or more microsatelli
te loci, suggesting that generalized MI may be a molecular manifestati
on of endometrial cancers. We next examined whether the MI was associa
ted 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 res
ults suggest the presence of multiple mutation subsets that act in a c
omplementary fashion in endometrial cancer development. (C) 1998 Acade
mic Press.