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Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions
  1. Stefanie Bertram1,
  2. Juliet Padden2,
  3. Julia Kälsch1,4,
  4. Maike Ahrens2,
  5. Leona Pott1,2,
  6. Ali Canbay4,
  7. Frank Weber3,
  8. Christian Fingas3,
  9. Andreas C Hoffmann5,
  10. Antonie Vietor1,
  11. Joerg F Schlaak4,
  12. Martin Eisenacher2,
  13. Henning Reis1,
  14. Barbara Sitek2,
  15. Hideo A Baba1
  1. 1Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
  2. 2Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany
  3. 3Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
  4. 4Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
  5. 5West German Cancer Center Essen, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
  1. Correspondence to Professor Hideo A Baba, Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany; hideo.baba{at}uk-essen.de

Abstract

Aims The distinction between intrahepatic cholangiocarcinoma (ICC) and benign bile duct lesions can be challenging. Using our previously identified potential biomarkers for ICC, we examined whether these are useful for the differential diagnosis of ICC, bile duct adenoma and reactive bile duct proliferations in an immunohistochemical approach and identified a diagnostic marker panel including known biomarkers.

Methods Subjects included samples from 77 patients with ICC, 33 patients with bile duct adenoma and 47 patients with ductular reactions in liver cirrhosis. Our previously identified biomarkers (stress-induced phosphoprotein 1 (STIP1), SerpinH1, 14-3-3Sigma) were tested immunohistochemically following comparison with candidates from the literature (cluster of differentiation 56, heat shock protein (HSP)27, HSP70, B-cell-lymphoma2, p53, ki67).

Results The expression of SerpinH1 and 14-3-3Sigma was significantly higher in ICC than in bile duct adenomas and ductular reactions (p<0.05), whereas STIP1 expression was significantly higher (p<0.05) in ICC than in ductular reactions, but the difference to the bile duct adenoma group was not significant. A panel of the biomarker SerpinH1, 14-3-3Sigma and ki67 (≥2 marker positive) showed a high diagnostic accuracy (sensitivity 87.8%, specificity 95.9%, accuracy 91.8%) in the differential diagnosis of ICC versus non-malignant bile duct lesions.

Conclusions This suggests that 14-3-3Sigma and SerpinH1 may be useful in the differential diagnosis of malignant, benign and reactive bile duct lesions in addition to ki67 where a cut-off of >5% might be used for the distinction of malignant and non-malignant lesions.

  • CHOLANGIOCARCINOMA
  • BILIARY
  • IMMUNOHISTOCHEMISTRY

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