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 beta-catenin and AXIN I genes, and immunohistochemistry for beta-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 beta-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 beta-catenin immunostaining was observed in 30 of 81 HCCs, but not in dysplastic nodules. CONCLUSION: Taken together, our data suggest that beta-catenin stabilization because of either beta-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.
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 beta-catenin and AXIN I genes, and immunohistochemistry for beta-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 beta-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 beta-catenin immunostaining was observed in 30 of 81 HCCs, but not in dysplastic nodules. CONCLUSION: Taken together, our data suggest that beta-catenin stabilization because of either beta-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.
Authors: Pal Kaposi-Novak; Louis Libbrecht; Hyun Goo Woo; Yun-Han Lee; Nathaniel C Sears; Cedric Coulouarn; Elizabeth A Conner; Valentina M Factor; Tania Roskams; Snorri S Thorgeirsson Journal: Cancer Res Date: 2009-03-10 Impact factor: 12.701