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- Publisher Website: 10.1002/1097-0142(20010701)92:1<136::AID-CNCR1301>3.0.CO;2-R
- Scopus: eid_2-s2.0-0035395236
- PMID: 11443619
- WOS: WOS:000169666200018
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Article: β-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance
Title | β-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance |
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Authors | |
Keywords | β-catenin Clinicopathologic correlation and prognostication Hepatocellular carcinoma Mutations Nuclear accumulation Overexpression |
Issue Date | 2001 |
Publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741 |
Citation | Cancer, 2001, v. 92 n. 1, p. 136-145 How to Cite? |
Abstract | BACKGROUND. β-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 β-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 β-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 β-catenin. Nuclear accumulation of the β-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 β-catenin overexpression may be heterogeneous. HCCs with a nonnuclear type of β-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 β-catenin mutations were more frequent in HCV-associated HCC than in HBV-associated ones. CONCLUSIONS, β-catenin mutation and deregulation may play an important role in hepatocarcinogenesis. Nonnuclear type β-catenin overexpression appeared to have pathologic and prognostic significance. © 2001 American Cancer Society. |
Persistent Identifier | http://hdl.handle.net/10722/148252 |
ISSN | 2023 Impact Factor: 6.1 2023 SCImago Journal Rankings: 2.887 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wong, CM | en_HK |
dc.contributor.author | Fan, ST | en_HK |
dc.contributor.author | Ng, IOL | en_HK |
dc.date.accessioned | 2012-05-29T06:11:48Z | - |
dc.date.available | 2012-05-29T06:11:48Z | - |
dc.date.issued | 2001 | en_HK |
dc.identifier.citation | Cancer, 2001, v. 92 n. 1, p. 136-145 | en_HK |
dc.identifier.issn | 0008-543X | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/148252 | - |
dc.description.abstract | BACKGROUND. β-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 β-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 β-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 β-catenin. Nuclear accumulation of the β-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 β-catenin overexpression may be heterogeneous. HCCs with a nonnuclear type of β-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 β-catenin mutations were more frequent in HCV-associated HCC than in HBV-associated ones. CONCLUSIONS, β-catenin mutation and deregulation may play an important role in hepatocarcinogenesis. Nonnuclear type β-catenin overexpression appeared to have pathologic and prognostic significance. © 2001 American Cancer Society. | en_HK |
dc.language | eng | en_US |
dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741 | en_HK |
dc.relation.ispartof | Cancer | en_HK |
dc.subject | β-catenin | en_HK |
dc.subject | Clinicopathologic correlation and prognostication | en_HK |
dc.subject | Hepatocellular carcinoma | en_HK |
dc.subject | Mutations | en_HK |
dc.subject | Nuclear accumulation | en_HK |
dc.subject | Overexpression | en_HK |
dc.subject.mesh | Adult | en_US |
dc.subject.mesh | Aged | en_US |
dc.subject.mesh | Amino Acid Sequence | en_US |
dc.subject.mesh | Base Sequence | en_US |
dc.subject.mesh | Carcinoma, Hepatocellular - Genetics - Metabolism - Mortality - Pathology | en_US |
dc.subject.mesh | Cytoskeletal Proteins - Biosynthesis - Genetics | en_US |
dc.subject.mesh | Dna - Analysis | en_US |
dc.subject.mesh | Dna Mutational Analysis | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Genetic Markers - Genetics | en_US |
dc.subject.mesh | Hepatitis B - Complications | en_US |
dc.subject.mesh | Hepatitis B Virus | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Liver Neoplasms - Genetics - Metabolism - Mortality - Pathology | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Middle Aged | en_US |
dc.subject.mesh | Molecular Sequence Data | en_US |
dc.subject.mesh | Mutation | en_US |
dc.subject.mesh | Prognosis | en_US |
dc.subject.mesh | Sequence Homology, Amino Acid | en_US |
dc.subject.mesh | Survival Analysis | en_US |
dc.subject.mesh | Trans-Activators | en_US |
dc.subject.mesh | Tumor Markers, Biological - Biosynthesis - Genetics | en_US |
dc.subject.mesh | Beta Catenin | en_US |
dc.title | β-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Wong, CM: jackwong@pathology.hku.hk | en_HK |
dc.identifier.email | Fan, ST: stfan@hku.hk | en_HK |
dc.identifier.email | Ng, IOL: iolng@hkucc.hku.hk | en_HK |
dc.identifier.authority | Wong, CM=rp00231 | en_HK |
dc.identifier.authority | Fan, ST=rp00355 | en_HK |
dc.identifier.authority | Ng, IOL=rp00335 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1002/1097-0142(20010701)92:1<136::AID-CNCR1301>3.0.CO;2-R | en_HK |
dc.identifier.pmid | 11443619 | - |
dc.identifier.scopus | eid_2-s2.0-0035395236 | en_HK |
dc.identifier.hkuros | 71991 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0035395236&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 92 | en_HK |
dc.identifier.issue | 1 | en_HK |
dc.identifier.spage | 136 | en_HK |
dc.identifier.epage | 145 | en_HK |
dc.identifier.isi | WOS:000169666200018 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Wong, CM=16314668400 | en_HK |
dc.identifier.scopusauthorid | Fan, ST=7402678224 | en_HK |
dc.identifier.scopusauthorid | Ng, IOL=7102753722 | en_HK |
dc.identifier.issnl | 0008-543X | - |