Molecular differences between RER+ and RER- sporadic endometrial carcinomas in a large population-based series

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society
N MacDonaldI J Jacobs

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-beta RII, 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-beta RII, 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...Continue Reading

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