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Mutations of β-catenin and AXIN I genes are a late event in human hepatocellular carcinogenesis


Cheol Keun Park, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Iwon-dong, Kangnam-gu, Seoul 135-710, Korea.
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Abstract: Background: Hepatocellular carcinoma (HCC) is a well-known cancer involving the Wnt pathway in its carcinogenesis.

Aims: However, it is not clear whether these genetic changes are early genetic events in hepatocarcinogenesis or not.

Method: In this study, we performed mutational analysis of the β-catenin and AXIN I genes, and immunohistochemistry for β-catenin in a series of 114 hepatocellular nodular lesions, including premalignant lesions such as low-grade dysplastic nodules (LGDNs) and high-grade dysplastic nodules (HGDNs). Results: In the present study, mutations of the β-catenin and AXIN I genes were detected in 16% (13 out of 81) and 6.2% (five of 81) of the HCCs, respectively. However, no mutations were found in 14 LGDNs and 19 HGDNs. Moreover, abnormal nuclear β-catenin immunostaining was observed in 30 of 81 HCCs, but not in dysplastic nodules.

Conclusion: Taken together, our data suggest that β-catenin stabilization because of either β-catenin or AXIN I mutation might be a late event for malignant progression rather than an early genetic event involving the initiation of HCC development.