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Article: β-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance

Titleβ-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance
Authors
Keywordsβ-catenin
Clinicopathologic correlation and prognostication
Hepatocellular carcinoma
Mutations
Nuclear accumulation
Overexpression
Issue Date2001
PublisherJohn 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?
AbstractBACKGROUND. 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 Identifierhttp://hdl.handle.net/10722/148252
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, CMen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2012-05-29T06:11:48Z-
dc.date.available2012-05-29T06:11:48Z-
dc.date.issued2001en_HK
dc.identifier.citationCancer, 2001, v. 92 n. 1, p. 136-145en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/148252-
dc.description.abstractBACKGROUND. 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.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_HK
dc.relation.ispartofCanceren_HK
dc.subjectβ-cateninen_HK
dc.subjectClinicopathologic correlation and prognosticationen_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectMutationsen_HK
dc.subjectNuclear accumulationen_HK
dc.subjectOverexpressionen_HK
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCarcinoma, Hepatocellular - Genetics - Metabolism - Mortality - Pathologyen_US
dc.subject.meshCytoskeletal Proteins - Biosynthesis - Geneticsen_US
dc.subject.meshDna - Analysisen_US
dc.subject.meshDna Mutational Analysisen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Markers - Geneticsen_US
dc.subject.meshHepatitis B - Complicationsen_US
dc.subject.meshHepatitis B Virusen_US
dc.subject.meshHumansen_US
dc.subject.meshLiver Neoplasms - Genetics - Metabolism - Mortality - Pathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshPrognosisen_US
dc.subject.meshSequence Homology, Amino Aciden_US
dc.subject.meshSurvival Analysisen_US
dc.subject.meshTrans-Activatorsen_US
dc.subject.meshTumor Markers, Biological - Biosynthesis - Geneticsen_US
dc.subject.meshBeta Cateninen_US
dc.titleβ-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significanceen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, CM: jackwong@pathology.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.authorityWong, CM=rp00231en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/1097-0142(20010701)92:1<136::AID-CNCR1301>3.0.CO;2-Ren_HK
dc.identifier.pmid11443619-
dc.identifier.scopuseid_2-s2.0-0035395236en_HK
dc.identifier.hkuros71991-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035395236&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume92en_HK
dc.identifier.issue1en_HK
dc.identifier.spage136en_HK
dc.identifier.epage145en_HK
dc.identifier.isiWOS:000169666200018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWong, CM=16314668400en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK

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