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Short Communications |
From the Unit of Molecular Pathology,*
International
Agency for Research on Cancer (IARC), Lyon, France; the First
Department of Surgery, Yamanashi University of Medical
School,
Yamanashi, Japan; and the Department
of Pathology,
Institute of Clinical
Pathology, University Hospital Zürich, Zürich, Switzerland
Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Hepatitis B virus and hepatitis C virus infections, exposure to aflatoxin, and excessive intake of alcohol have been identified as major risk factors. However, the molecular mechanisms underlying their development are still poorly understood. Recently, ß-catenin, one of the key components of the Wnt signaling pathway, has been found to be mutated in about 20% of HCCs, suggesting a role of the Wnt pathway in their development. In this study, we examined ß-catenin and APC mutations in 22 HCCs associated with HCV infection, using single-strand conformation polymorphism (SSCP) followed by direct DNA sequencing. ß-Catenin mutations were found in nine (41%) cases, but no APC mutations were found. ß-Catenin immunohistochemistry revealed nuclear accumulation of ß-catenin protein in all nine tumors with a ß-catenin mutation and two additional tumors without a mutation. These results suggest that activation of the Wnt signaling pathway by ß-catenin mutation contributes significantly to the hepatocellular carcinogenesis associated with HCV infection.
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