Expression of Wnt-5a and β-catenin in primary hepatocellular carcinoma.

It has been reported that changes in Wnt5a expression are closely related to hepatocellular carcinoma (HCC) development, while decreased or abnormal β-catenin expression may promote the invasion and metastasis of tumor cells. In this study, the roles and clinical significance of Wnt-5a and β-catenin expression were analyzed in primary HCC. Real-time PCR (RT-PCR) analysis of Wnt-5a mRNA expression was performed in 26 fresh HCC samples and the corresponding para-carcinoma tissues. Wnt-5a and β-catenin protein expression was detected by immunohistochemical staining of paraffin-embedded tissues of 85 cases of HCC and corresponding para-carcinoma tissues and 15 cases of hepatic cirrhosis. Results showed that Wnt-5a mRNA levels were significantly higher in HCC tissue than in the para-carcinoma tissue (0.102 ± 0.159 and 0.020 ± 0.022, respectively; P < 0.05), while Wnt-5a protein was absent or low in HCC. Wnt-5a expression was detected in significantly fewer HCC tissue samples than in the para-carcinoma and hepatic cirrhosis tissue samples (21.2% (18/85), 81.26% (69/85) and 86.7% (13/15), respectively; P < 0.01). Abnormal localization of β-catenin protein shown by intracytoplasmic or intranuclear staining was observed in 72.94% (62/85) of HCC samples. These observations indicate that the role of Wnt-5a in HCC is mediated at the protein level rather than the transcriptional level. Furthermore, the abnormal localization of β-catenin observed in HCC tissues may be associated with gene mutation leading to the generation of truncated β-catenin proteins, which in turn, may represent an initiating or contributing factor in the development of HCC.