title: Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis.
abstract: Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used.
  
  
  CONCLUSIONS
  The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis.
authors.affiliation: Department of Pathology, University of Milan School of Medicine and IRCCS Humanitas Clinical Institute, Rozzano, Milan, Italy, and Institute of Pathology, University Hospital Basel, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
authors.forename: Giada
authors.initials: G
authors.lastname: Franchi
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.forename: Barbara
authors.initials: B
authors.lastname: Fiamengo
authors.forename: Annarita
authors.initials: A
authors.lastname: Destro
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morenghi
authors.forename: Marco
authors.initials: M
authors.lastname: Montorsi
authors.forename: Guido
authors.initials: G
authors.lastname: Torzilli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tommasini
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Vecchione
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D053673:Glypicans / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C105937:GPC3 protein, human; D053673:Glypicans; D018840:HSP70 Heat-Shock Proteins; D005974:Glutamate-Ammonia Ligase