β-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis

Hey Chi Hsu, Yung Ming Jeng, Tsui Lien Mao, Jan-Show Chu, P. L. Lai, S. Y. Peng

Research output: Contribution to journalArticle

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Abstract

To better understand the role of β-catenin mutation in hepatocellular carcinoma (HCC), we correlated the gene mutation with hepatitis virus B (HBV) and hepatitis virus C (HCV) status and the clinicopathological features in 366 patients with resected primary unifocal HCC. β-Catenin mutations were also analyzed in 55 patients with multifocal HCC (68 tumors). Of the whole series, 57 (13.1%) of 434 tumors examined had β-catenin mutations, 34 occurred at the serine/threonine residues of the GSK-3β region of β-catenin. Outside the GSK-3β phosphorylation site, codons 32 and 34 were two mutational hot spots (17 tumors). The non-HBV-related HCC that was predominantly HCV related had a higher frequency of mutation (P <0.00001) and more frequent mutations at codon 45 than HBV-related HCC. HBV-related HCC had a younger mean age (P <0.00001), and higher male-to-female ratio (P <0.003) and positive familial history of HCC (P <0.014). Among 366 unifocal HCCs selected for clinicopathological analysis, β-catenin mutations were associated with grade I (P = 0.005) and stage I and II HCC (P <0.0001), and a better 5-year survival rate (P = 0.00003). These findings suggest mechanisms for β-catenin mutations differ between HBV-related and non-HBV-related HCCs, and that β-catenin mutation is a favorable prognostic factor related to low stage. β-Catenin mutation was associated with nuclear expression of the protein (P <0.00001), but we failed to detect point or large fragment deletion mutation in 39 HCCs with nuclear β-catenin expression, presumably wild-type protein. HCCs expressing mutant nuclear β-catenin had a better 5-year survival rate (P <0.007), suggesting that mutant and wild-type nuclear β-catenin proteins are not functionally equivalent and deserve more studies for further clarification.

Original languageEnglish
Pages (from-to)763-770
Number of pages8
JournalAmerican Journal of Pathology
Volume157
Issue number3
Publication statusPublished - 2000
Externally publishedYes

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Catenins
Hepatitis B virus
Hepatocellular Carcinoma
Mutation
Glycogen Synthase Kinase 3
Hepatitis Viruses
Nuclear Proteins
Codon
Survival Rate
Cercopithecine Herpesvirus 1
Neoplasms
Sequence Deletion
Mutation Rate
Threonine
Hepatitis C
Serine
Phosphorylation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

β-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. / Hsu, Hey Chi; Jeng, Yung Ming; Mao, Tsui Lien; Chu, Jan-Show; Lai, P. L.; Peng, S. Y.

In: American Journal of Pathology, Vol. 157, No. 3, 2000, p. 763-770.

Research output: Contribution to journalArticle

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