title: Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bertram
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Juliet
authors.initials: J
authors.lastname: Padden
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kälsch
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Ahrens
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Leona
authors.initials: L
authors.lastname: Pott
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Weber
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Fingas
authors.affiliation: West German Cancer Center Essen, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Hoffmann
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Antonie
authors.initials: A
authors.lastname: Vietor
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000236:Adenoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001649:Bile Duct Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005095:Exoribonucleases / Q000378:metabolism; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494660:SERPINH1 protein, human; C079373:STIP1 protein, human; D005095:Exoribonucleases; C413442:SFN protein, human
keywords: BILIARY; CHOLANGIOCARCINOMA; IMMUNOHISTOCHEMISTRY