Cancer  2001 Jul 1;92(1):136-45 

beta-Catenin mutation and overexpression in hepatocellular carcinoma:
clinicopathologic and prognostic significance.

Wong CM, Fan ST, Ng IO.

Department of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam,
Hong Kong.

BACKGROUND: beta-Catenin has been recognized as a critical member of the Wnt
signaling pathway, and inappropriate activation of this pathway has been
implicated in carcinogenesis. METHODS: To determine the clinical significance of
beta-catenin in hepatocellular carcinoma (HCC), we performed mutational analysis
at exon 3 of the gene, investigated the subcellular protein expression, and
analyzed their clinicopathologic and prognostic significance in 60 patients with
resected primary HCC. RESULTS: By direct DNA sequencing, somatic mutations of
the beta-catenin gene were detected in 7 (12%) HCCs. All the mutations were
found at the region (exon 3) responsible for phosphorylation and ubiquitination,
therefore likely to result in stabilization of free cytoplasmic beta-catenin.
Nuclear accumulation of the beta-catenin protein, similar to the response to the
Wnt signal, was found in 10 (17%) HCCs and was closely associated with gene
mutation (P < 0.001). In the remaining cases, nonnuclear type overexpression,
that is, overexpression in the cytoplasm and/or cytoplasmic membrane, was
observed in 31 (62%) HCCs, thus suggesting that the mechanisms leading to
beta-catenin overexpression may be heterogeneous. HCCs with a nonnuclear type of
beta-catenin overexpression were more frequently larger than 5 cm in diameter (P
= 0.022) and had poorer cellular differentiation (P = 0.037), and the patients
had significantly shorter disease-free survival lengths (P = 0.041). Review of
the data from previous studies in HCC showed that beta-catenin mutations were
more frequent in HCV-associated HCC than in HBV-associated ones. CONCLUSIONS:
beta-catenin mutation and deregulation may play an important role in
hepatocarcinogenesis. Nonnuclear type beta-catenin overexpression appeared to
have pathologic and prognostic significance. Copyright 2001 American Cancer
Society.

PMID: 11443619 [PubMed - indexed for MEDLINE]