The role of hMSH3 and hMSH6 in ovarian endometrioid carcinoma and relationship with microsatellite instability phenotype

Abstract

Frequent frameshift mutations in the DNA mismatch repair genes hMSH3, and hMSH6, have been reported in colorectal and endometrial cancers with microsatellite instability, however, it is unclear whether they are similarly altered in ovarian endometrioid carcinoma. In this study, we examined frequency of frameshift mutation and protein expression in hMSH3 and hMSH6 in ovarian endometrioid carcinoma with or without microsatellite instability. Only 1 frameshift mutation of the 16 cases with microsatellite instability-high phenotype (6%) was detected in poly(A)8 tract of the hMSH3, but not in poly(C)8 tract of hMSH6 genes. In addition, none of the 6 microsatellite instability-low or 20 microsatellite-stable tumors showed mutations in these regions in either gene. These results indicate that mutations in the mono-nucleotide tracts of hMSH3 and hMSH6 are infrequent in ovarian endometrioid adenocarcinomas, other mechanisms may play a more important role in the development of these tumors.