Altered distribution of beta-catenin and prognostic roles in colorectal carcinogenesis

Although beta-catenin cytoplasmic stabilization and nuclear translocation play a key role in initiation of colorectal cancer (CRC), the mechanisms are far from clear. The aim of this study was to investigate the relation of expressions of cyclooxygenase (COX)-2 and E-cadherin, and the beta-catenin gene exon 3 mutation to the altered distribution of beta-catenin, and their roles in CRC progression and prognosis.

Expressions of beta-catenin, COX-2 and E-cadherin in 96 tissue specimens were detected by immunohistochemistry, and mutation of beta-catenin gene exon 3 was screened by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC).

Cytoplasmic/nuclear expression of beta-catenin and reduced membranous expression of E-cadherin were associated, respectively, with the earlier and later stages of sequential colorectal carcinogenesis (p<0.05). The altered distribution of beta-catenin was significantly associated with both high Dukes' stages and poor differentiation of CRC (p<0.05). It also had a parallel relationship with COX-2 overexpression (p<0.05, Spearman's rank analysis), but not with reduced E-cadherin expression. Kaplan-Meier analysis showed a significantly worse survival rate for CRC patients with altered expression of beta-catenin (p<0.05, log-rank test). Nevertheless, we failed to find any exon 3 mutation of beta-catenin gene in all 60 cases of CRC.

Altered distribution of beta-catenin occurs in the early stage of colorectal carcinogenesis and has a parallel relationship with COX-2 overexpression. It may serve as a potential marker for the progression and prognosis of CRC. The exon 3 mutation did not appear contributive to the abnormal expression of beta-catenin in CRCs in a Chinese population.