Document Detail

Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma.
MedLine Citation:
PMID:  22287594     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND AIMS: Conventional pathological analysis fails to achieve sufficient sensitivity and specificity for the diagnosis of hepatocellular carcinoma (HCC) in small nodules. Immunohistochemical staining for glypican 3 (GPC3), heat shock protein 70 (HSP70) and glutamine synthetase (GS) has been suggested to allow a confident diagnosis but no prospective study has established the diagnostic accuracy of this approach. The aim of this study is to assess prospectively the diagnostic accuracy of a panel of markers (GPC3, HSP70, GS) for the diagnosis of HCC in patients with cirrhosis with a small (5-20 mm) nodule detected by ultrasound screening.
METHODS: Sixty patients with cirrhosis with a single nodule 5-20 mm newly detected by ultrasound were included in the study. Contrast-enhanced ultrasound, magnetic resonance and fine needle biopsy of the nodule (gold standard) were performed; the biopsy was repeated in case of diagnostic failures. Three consecutive sections of the first biopsy sample with meaningful material were stained with antibodies against GPC3, HSP70 and GS.
RESULTS: Forty patients were diagnosed with HCC. The sensitivity and specificity for HCC diagnosis were: GPC3 57.5% and 95%, HSP70 57.5% and 85%, GS 50% and 90%, respectively. The sensitivity and specificity of the different combinations were: GPC3+HSP70 40% and 100%; GPC3+GS 35% and 100%; HSP70+GS 35% and 100%; GPC3+HSP70+GS 25% and 100%. When at least two of the markers were positive (regardless of which), the sensitivity and specificity were 60% and 100%, respectively. Conventional pathological analysis yielded three false negative results, but the addition of this panel only correctly classified one of these cases as HCC.
CONCLUSION: These data within a prospective study establish the clinical usefulness of this panel of markers for the diagnosis of early HCC. However, the panel only slightly increases the diagnostic accuracy in an expert setting.
Silvia Tremosini; Alejandro Forner; Loreto Boix; Ramon Vilana; Luis Bianchi; Maria Reig; Jordi Rimola; Carlos Rodríguez-Lope; Carmen Ayuso; Manel Solé; Jordi Bruix
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2012-01-27
Journal Detail:
Title:  Gut     Volume:  61     ISSN:  1468-3288     ISO Abbreviation:  Gut     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-10     Completed Date:  2012-11-19     Revised Date:  2013-11-18    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  1481-7     Citation Subset:  AIM; IM    
Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain.
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MeSH Terms
Biopsy, Fine-Needle
Carcinoma, Hepatocellular / diagnosis*,  metabolism,  ultrasonography
Early Detection of Cancer / methods*
Glutamate-Ammonia Ligase / metabolism*
Glypicans / metabolism*
HSP70 Heat-Shock Proteins / metabolism*
Liver / metabolism,  pathology,  ultrasonography
Liver Neoplasms / diagnosis*,  metabolism,  ultrasonography
Middle Aged
Prospective Studies
Sensitivity and Specificity
Tumor Markers, Biological / metabolism*
Reg. No./Substance:
0/GPC3 protein, human; 0/Glypicans; 0/HSP70 Heat-Shock Proteins; 0/Tumor Markers, Biological; EC Ligase
Comment In:
Gut. 2013 Oct;62(10):1520-1   [PMID:  23929696 ]
Gut. 2013 Mar;62(3):477-8   [PMID:  23013726 ]
Gut. 2012 Oct;61(10):1514-5   [PMID:  22851668 ]
Gut. 2013 Nov;62(11):1667-8   [PMID:  23708586 ]

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