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(American Journal of Pathology. 1999;155:1795-1801.)
© 1999 American Society for Investigative Pathology

Short Communications

ß-Catenin Mutations Are Frequent in Human Hepatocellular Carcinomas Associated with Hepatitis C Virus Infection

Huatao Huang*, Hideki Fujii{dagger}, Anna Sankila*, Betania M. Mahler-Araujo*, Masanori Matsuda{dagger}, Gieri Cathomas{ddagger} and Hiroko Ohgaki*

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,{dagger}
Yamanashi, Japan; and the Department of Pathology,{ddagger}
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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