title: Role of CD15 expression in dysplastic and neoplastic tissue of the bile duct - a potential novel tool for differential diagnosis of indeterminate biliary stricture.
abstract: OBJECTIVE
  CD15 is expressed by various cancer types; among these are intrahepatic and perihilar cholangiocarcinoma (CCA). The aim of this study was to elucidate CD15 expression in distal CCA as well as in dysplastic biliary tissue and to determine its prognostic significance.
  
  
  RESULTS
  Tissue samples from patients with intrahepatic (iCCA, n = 22), perihilar (pCCA, n = 7) and distal CCA (dCCA, n = 15), who underwent surgical resection in the period from 2010 to 2015 were evaluated for CD15 expression. Tissue of synchronous lymph node metastasis (n = 13), CCA-associated dysplasia (n = 20), dysplasia in intraductal biopsies (n = 10) and benign proliferations (n = 12), as well as inflammatory biliary lesions (n = 28) and non-inflammatory bile ducts (n = 23), were evaluated equally for CD15 expression. CD15 was found to be expressed highly in iCCA (81.8%), pCCA (85.7%), dCCA (73.3%), CCA-associated dysplasia (70.0%), dysplasia in intraductal biopsies (100%) and metastatic tissue (84.6%). CD15 expression was negative in 58 of 64 benign bile duct alterations resulting in an overall sensitivity and specificity of CD15 in CCA of 80.7 and 90.6% patients, respectively. CD15 expression was correlated significantly with a decreased overall survival in patients with CD15-positive CCA associated dysplasia (P = 0.003). However, CD15 expression in the invasive tumour component was not correlated with clinical outcome.
  
  
  CONCLUSIONS
  CD15 is a sensitive and specific marker for intraepithelial and invasive neoplasias of the bile duct. Therefore, it can be helpful in the delineation of dysplastic and neoplastic biliary cells from non-neoplastic tissue, which frequently causes a diagnostic problem in indeterminate biliary stricture.
authors.affiliation: Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Dirk
authors.identifier: http://orcid.org/0000-0003-2309-9624
authors.initials: D
authors.lastname: Walter
authors.affiliation: Institute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: Dr Senckenberg Institute of Pathology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Ria
authors.initials: R
authors.lastname: Winkelmann
authors.affiliation: Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Jörg G
authors.initials: JG
authors.lastname: Albert
authors.affiliation: Department of General and Visceral Surgery, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Liese
authors.affiliation: Department of General and Visceral Surgery, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schnitzbauer
authors.affiliation: Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Dr Senckenberg Institute of Pathology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.affiliation: Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Peveling-Oberhag
authors.affiliation: Dr Senckenberg Institute of Pathology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis*; D001652:Bile Ducts / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000175:diagnosis*; D003251:Constriction, Pathologic; D003937:Diagnosis, Differential; D005260:Female; D005647:Fucosyltransferases / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D016256:Lewis X Antigen / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D016256:Lewis X Antigen; C066693:FUT4 protein, human; D005647:Fucosyltransferases
keywords: CD15; Lewis X; cholangiocarcinoma; dysplasia; indeterminate biliary stricture; metastasis