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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
  1. Silvia Tremosini1,
  2. Alejandro Forner1,2,
  3. Loreto Boix1,2,
  4. Ramon Vilana2,3,
  5. Luis Bianchi2,3,
  6. Maria Reig1,2,
  7. Jordi Rimola2,3,
  8. Carlos Rodríguez-Lope1,
  9. Carmen Ayuso2,3,
  10. Manel Solé2,4,
  11. Jordi Bruix1,2
  1. 1Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
  2. 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
  3. 3Radiology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
  4. 4Pathology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
  1. Correspondence to Jordi Bruix, BCLC Group, Liver Unit, IMDM, Hospital Clínic, c/ Villarroel 170, Escala 11, 4° Planta, 08036 Barcelona, Spain; jbruix{at}


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.

  • Hepatocellular carcinoma
  • glypican 3
  • heat shock protein 70
  • glutamine synthetase
  • immunohistochemistry
  • diagnosis
  • hepatocellular carcinoma
  • haemochromatosis
  • HCV
  • cirrhosis
  • cancer
  • hepatobiliary cancer
  • abdominal mri
  • hepatoma
  • liver transplantation
  • liver
  • liver failure
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  • The content of this work was presented in abstract form at the ILCA 5th Annual Conference in September 2011 and the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) 2011.

  • ST and AF contributed equally to this work.

  • Funding This study was supported by grants from the Instituto de Salud Carlos III (PI 06/132 and PI 08/0146). CIBEREHD is funded by Instituto de Salud Carlos III. ST was partially supported by a grant from the BBVA Foundation. MR was partially supported by a grant from the University of Barcelona (APIF RD63/2006). CR-L was supported by a grant of the Instituto de Salud Carlos III (FI09/00510).

  • Competing interests None.

  • Ethics approval This study was approved by the Ethics Committee for Clinical Research, Hospital Clínic Barcelona, Spain and written informed consent was obtained from each patient.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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