Evaluation of microsatellite instability, MLH1 expression and hMLH1 promoter hypermethylation in colorectal carcinomas among Tunisians patients.

Background: About 10% to 15% of sporadic colorectal cancers demonstrate high level of microsatellite instability that is generally associated with aberrant methylation of hMLH1 promoter.

Aim: To investigate the association between MSI status, hMLH1 protein expression and methylation status of the hMLH1 promoter in a cohort of Tunisian sporadic colorectal cancer.

Methods: Expression of MLH1 and MSH2 was determined by immunohistochemistry and the MSI status was analysed by microfluid-based on-chip electrophoresis. Methylation of the hMLH1 gene promoter was determined by methylation-specific PCR.

Results: Of the 150 colorectal cancers 57% were MSS, 28% were MSI-L and 15%were MSI-H. MSI-H tumors were more frequently right-sided, exhibited a stage III of TNM and tended more to be mucinous. The MSI status had no effect on overall patient survival. Most of the MSS/MSI-L 79% cancers were unmethylated at the hMLH1 promoter, while 26% MSI-H cancers were unmethylated. 84% of MSS and MSI-L expressed MLH1 and 52% of MSI-H expressed MLH1. Of the methylated MSI-H cases, 35% expressed MLH1 protein while 100% of the unmethylated MSI-H were positive for MLH1 staining. Of 11 MSI-H cancers with loss of MLH1 expression, all cases were also methylated while 50% MSI-H cancers with positive immunostaining for MLH1 were methylated at the hMLH1 promoter.

Conclusion: Our study showed that MSI-H phenotype was mucinous, right-side and exhibit stade III of TNM. The relative correlation of MLH1 expression and promotor hypermethylation of hMLH1 for the MSI status is similar to that reported for several study.