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

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

[Epidemiological study, pathologic evaluation and prognostic factors of colorectal mucinous adenocarcinoma VS non mucinous [about a series of 196 patients]]

Colorectal carcinoma is one of the main causes of cancer death in the worldwide with a decrease survival rate in relationship with a later diagnosis of advanced disease. This study highlights the particular epidemiological, clinicopathological and immunohistochemical colorectal cancer profile. Indeed, our results differ markedly from that reported in the literature. We underwent a retro and prospective study interesting 196 patients with colorectal carcinoma diagnosed in the pathological and cytological laboratory of Mongi Slim Hospital [Tunisia]. Age at diagnosis, mode of presentation, sex, tumour location, macroscopic and histological features, TNM and Astler Coller stage were assessed and evaluated. we report here a particular epidemiological pattern which is characterised by younger age of the patients, equally distribution between men and women, predominant sporadic carcinomas and preponderance of rectosigmoid location. The poorer degree of differentiation and mucinous subtype are correlated with an advanced stage. It is also correlated with more frequent vascular embols, neural invasion and metastatic nodes. Furthermore, immunohistochemical analysis of galectin-3 showed a significant difference between mucinous and non mucinous adenocarcinoma. Based on the presented data, the epidemiological pattern and the anatomic distribution especially in the rectosigmoid region suggest diet and lifestyle to be primordial risk factors of colorectal tumorigenesis

[Pulmonary lymphangiomatosis revealed by an interstitial syndrome in a young adult]

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