Mismatch DNA Repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA Expression Profiles in Colorectal Carcinomas

Background: Mismatch repair (MMR) deficiency has been related with HNPCCs. So far, there is limited information on MMR mRNA profiles in sporadic colorectal carcinomas (CRCs). We previously showed that distinct MMR mRNA phenotypes were related to tumor stage and survival of patients with lung cancer or urinary bladder carcinomas. Aim: The aim of this study was to quantify hMSH2, hMLH1, hMSH6 and hPMS2 mRNA levels, in CRCs and their adjacent normal tissues (ANTs), using accurate methodology, and to correlate MMR mRNA profiles with patient or tumor characteristics. Materials and methods: We analyzed 31 fresh frozen tissue specimens of paired CRCs with their ANTs. We evaluated MMR mRNA profiles by a Q-real-time PCR, using hPBGD gene as reference control and creating a standard curve. The MMR mRNA levels were assigned as ratios MMR/hPBGD mRNAs. Relative expression of each MMR gene was given as ratios of CRCs/ANTs mRNA levels. Results: All CRCs and their ANTs expressed low hPMS2 mRNA levels while a significant proportion of CRCs (73%) and their ANTs (82%) presented low hMSH2 mRNA levels. Analysis of relative expression patterns showed that hMSH6 and hMLH1 exhibited the highest percentages of reduction (53% and 45.5%, respectively). We found a correlation of transcriptional levels between hMSH2 and hMLH1, the crucial components of MMR mechanism and between their counterparts, hMSH6 and hPMS2, in CRCs of early stages, related to gender. On the contrary, CRCs of late stages revealed a correlation between reduced levels of hMSH2 and hMSH6, MutSa components, unrelated to gender but related to lymph node metastasis. Also, reduced hMSH2, hMSH6 and hMLH1 mRNA phenotypes correlated with advanced stage, and rectal localization. Conclusion: In this study we demonstrated that MMR mRNA deficiency is a common event in sporadic CRCs. Specific profiles of MMR deficiency maybe related to tumor progression, especially in male patients.