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The Prognostic Value of the Immunohistochemical Expression and Mutational Pattern of the Key Mediator of Wnt Signaling: Beta-catenin in Tunisian Patients With Colorectal Carcinoma

Beta-catenin plays a critical role with E-cadherin in cell-cell adhesion and is also a key molecule of the highly conserved Wnt signaling pathway that regulates cell proliferation and differentiation. Abrogation of this pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer. The objective of this study was to determine the prognostic value of &bgr;-catenin/E-cadherin complex in Tunisian patients with colorectal cancer. Matched primary tumors from 150 patients with sporadic colorectal adenocarcinomas were stained for &bgr;-catenin and E-cadherin by using immunohistochemistry. Deletion of exon 3 of CTNNB1 gene was performed by polymerase chain reaction. Our results showed that &bgr;-catenin and E-cadherin expressions were related inversely to tumor differentiation. Furthermore, the nuclear expression of &bgr;-catenin was considerably increased in advanced colorectal adenocarcinomas and was highly associated with shorter survival of patients. Deletion of exon 3 of CTNNB1 was identified in 2 cases by using polymerase chain reaction and was significantly related to tumor invasion and aberrant expression of E-cadherin. The major finding of this study is that activation of &bgr;-catenin gene by deletions involving exon 3 may be considered as an advanced event in colorectal tumorigenesis in Tunisian patients, in contrast to some worldwide studies. Moreover, disruption of &bgr;-catenin/E-cadherin complex may be considered as a dependent predictor of disease outcome.