Expression of beta-catenin in hepatocellular carcinoma in relation to tumor cell proliferation and cyclin D1 expression.

Alteration of beta-catenin expression has been implicated in the development of hepatocellular carcinoma (HCC). It has been also reported that beta-catenin can influence the tumor cell proliferation or cyclin D1 expression, one of the target factors of betacatenin. We performed an immunohistochemical analysis of beta-catenin and cyclin D1 in 77 patients with resected HCCs, and examined the relationships between the expressions of beta-catenin and cyclin D1, and other pathologic parameters including the mitotic index. Altered expressions of beta-catenin including nonnuclear overexpression and nuclear expression were detected in 58.4% of HCCs (45/77) and showed significant correlations with large tumor size, poor histologic grade, and high tumor stage. The mean mitotic index of HCCs with nuclear expression (3.2 +/- 3.0) and nonnuclear overexpression (2.7 +/- 2.5) was significantly higher than that of tumors with no overexpression (1.7 +/- 1.4) (p=0.018 and 0.038, respectively), however, no correlation was noted between the expressions of cyclin D1 and beta-catenin. In addition, nonnuclear overexpression out of two altered expression patterns was more frequent (37.7% versus 20.8%) as well as pathologically more significant than nuclear expression. These results indicate that the altered expression of beta-catenin in HCC may play an important role in tumor progression by stimulating tumor cell proliferation, and nonnuclear overexpression may have pathologic significance in HCC.