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

BCLC Group, Liver Unit, IMDM, Hospital Clínic, c/ Villarroel 170, Escala 11, 4° Planta, 08036 Barcelona, Spain
Gut (Impact Factor: 14.66). 01/2012; 61(10):1481-7. DOI: 10.1136/gutjnl-2011-301862
Source: PubMed


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.
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.
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.
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.

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    • "Its expression was observed in 282 of 392 HCC cases (71.9%), whereas only 14 of 115 non-neoplastic liver tissues expressed HSP70 (P<0.001) (9). The sensitivity and specificity in detecting HCC were identified as 57.5 and 85%, respectively (10). Furthermore, the expression of HSP70 is correlated with differentiation and apoptosis of tumor cells. "
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