title: DMBT1 expression in biliary carcinogenesis with correlation of clinicopathological data.
abstract: OBJECTIVE
  Deleted in malignant brain tumours 1 (DMBT1) exerts functions in the regulation of epithelial differentiation and inflammation and has been proposed as a tumour suppressor. Because chronic inflammation is a hallmark of cholangiocarcinogenesis, the aim of this study was to investigate the expression of DMBT1 in biliary tract cancer (BTC) and to correlate this expression with clinicopathological data.
  
  
  RESULTS
  The expression of DMBT1 protein was examined immunohistochemically in 157 BTC patients [41 intrahepatic (ICC), 60 extrahepatic cholangiocarcinomas (ECC) and 56 adenocarcinomas of the gallbladder (GBAC)]. Additionally, 56 samples of high-grade biliary intraepithelial neoplasia (BilIN 3) and 92 corresponding samples of histological non-neoplastic biliary tract tissues were included. DMBT1 expression was increased significantly in BilIN 3 compared to normal tissue (P < 0.0001) and BTC (P < 0.0001). BTC showed no significant difference in DMBT1 expression compared to non-neoplastic biliary tissue (P = 0.315). Absent DMBT1 expression in non-neoplastic biliary tissue of BTC patients was associated with poorer survival (P = 0.027). DMBT1 expression was correlated significantly with patients' age (P < 0.001).
  
  
  CONCLUSIONS
  DMBT1 is expressed differently in cholangiocarcinogenesis and poorer patients' survival rates are associated with absent DMBT1 expression in non-neoplastic biliary tissue, suggesting a tumour-suppressive role of DMBT1 in early cholangiocarcinogenesis.
authors.affiliation: Institute of Pathology, University Hospital, Heidelberg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Goeppert
authors.affiliation: Institute of Pathology, University Hospital, Heidelberg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Roessler
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Becker
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Oslo Center for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.affiliation: Diagnostic and Interventional Radiology, Thoraxklinik, University Hospital Heidelberg, Germany.
authors.forename: Monika N
authors.initials: MN
authors.lastname: Vogel
authors.affiliation: Institute of Pathology, University Hospital, Heidelberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, University Hospital Heidelberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Pathil-Warth
authors.affiliation: Department of General Visceral and Transplantation Surgery, University Hospital Heidelberg, Germany.
authors.forename: Arianeb
authors.initials: A
authors.lastname: Mehrabi
authors.affiliation: Institute of Pathology, University Hospital, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Molecular Oncology and Lundbeckfonden Center of Excellence NanoCAN, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
authors.affiliation: Institute of Pathology, University Hospital, Heidelberg, Germany.
authors.forename: Marcus
authors.identifier: http://orcid.org/0000-0001-6835-6300
authors.initials: M
authors.lastname: Renner
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D001661:Biliary Tract Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins
keywords: DMBT1; biliary tract cancer; extrahepatic cholangiocarcinoma; intrahepatic cholangiocarcinoma