title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tremosini
authors.forename: Alejandro
authors.initials: A
authors.lastname: Forner
authors.forename: Loreto
authors.initials: L
authors.lastname: Boix
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilana
authors.forename: Luis
authors.initials: L
authors.lastname: Bianchi
authors.forename: Maria
authors.initials: M
authors.lastname: Reig
authors.forename: Jordi
authors.initials: J
authors.lastname: Rimola
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodríguez-Lope
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Manel
authors.initials: M
authors.lastname: Solé
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D044963:Biopsy, Fine-Needle; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D053673:Glypicans / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014463:Ultrasonography
chemical_list: D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D018840:HSP70 Heat-Shock Proteins; D005974:Glutamate-Ammonia Ligase