Abstract

Studies, to date, have suggested that there are distinct molecular differences between microsatellite stable (RER^–) and unstable (RER⁺) solid tumors, such as colorectal carcinoma. We investigated a range of molecular events including mutation frequency of K-ras, microsatellite instability within the coding region of TGF-βRII, BAX, and IGF-IIR, loss of expression of p53, hMLH1, hMSH2, hMSH6, and PTEN, and methylation of hMLH1, hMSH2, and PTEN within a large population-based series of sporadic endometrial carcinomas to establish whether there are distinct differences between replication error repair (RER⁺) and RER^– cases. RER⁺ endometrial carcinomas tended to be diploid with normal p53 expression, compared with RER^– cases. Mutations in TGF-βRII, IGF-IIR, and BAX were rare, but there was a strong association between mutation and RER⁺ status. Methylation and loss of hMLH1 expression were significantly more common in RER⁺ cases, as was methylation of PTEN. K-ras mutations were equally frequent in RER⁺ and RER^– cases. Despite the absence of distinct clinicopathological differences between RER⁺ and RER^– cases in this series of sporadic endometrial carcinomas, our results confirm that there are molecular differences between RER⁺ and RER^– cases, but the molecular events occurring in RER⁺ endometrial carcinomas differ from those seen in RER⁺ colorectal carcinomas.