ABSTRACT
About 10% to 15% of sporadic colorectal cancers demonstrate high level of microsatellite instability that is generally associated with aberrant methylation of hMLH1 promoter. 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. Expression of MLH1 and MSH2 was determined by immunohistochemestry and the MSI status was analysed by microfluid-based on-chip electrophoresis. Methylation of the hMLH1 gene promoter was determined by methylation-specific PCR. Of the 140 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. Our study showed that MSI-H phenotype was mucinous, right-side and exhibit stade III of TNM. The relative correlation of MLH1 expression and promoter hypermethylation of hMLH1 for the MSI status is similar to that reported for several study
ABSTRACT
The p73 gene encodes a nuclear protein that is highy homologous to p53. p73 also shares some common functions with p53 protein indicating that p73 gene is a p53-like tumor suppressor. In this study, we examined by immunohistochemistry the p73 expression on 120 cases of colorectal carcinomas and evaluated its implication in carcinogenesis. Retrospective study. The results show an increase of intensity and distribution of p73 in common adenocarcinoma from the normal mucosa, to primary tumors and to metastases. However, in mucinous adenocarcinomas, immunostaining of p73 decrease in primary tumor and completely diseappears in isolated cells and metastases compared with matched normal mucosa. These observations are further reinforced by the fact that in adenocarcinoma with mucinous component less than 50%, the positivity of p73 persist in well-differentiated areas and dramatically decreases or completely deseappears in mucinous areas. In conclusion, p73 would be a prognosic marker for the common adenocarcinomas and an ethiopathogenic factor for the mucinous subtype