Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis.
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.
Di Tommaso
Luca
L
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.
Franchi
Giada
G
Park
Young Nyun
YN
Fiamengo
Barbara
B
Destro
Annarita
A
Morenghi
Emanuela
E
Montorsi
Marco
M
Torzilli
Guido
G
Tommasini
Maurizio
M
Terracciano
Luigi
L
Tornillo
Luigi
L
Vecchione
Raffaella
R
Roncalli
Massimo
M
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
D015415:Biomarkers; C105937:GPC3 protein, human; D053673:Glypicans; D018840:HSP70 Heat-Shock Proteins; D005974:Glutamate-Ammonia Ligase