DMBT1 expression in biliary carcinogenesis with correlation of clinicopathological data

Histopathology. 2017 Jun;70(7):1064-1071. doi: 10.1111/his.13175. Epub 2017 Mar 28.

Abstract

Aims: 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.

Methods and 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).

Conclusion: 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.

Keywords: DMBT1; biliary tract cancer; extrahepatic cholangiocarcinoma; intrahepatic cholangiocarcinoma.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology*
  • Biliary Tract Neoplasms / metabolism
  • Biliary Tract Neoplasms / mortality
  • Biliary Tract Neoplasms / pathology*
  • Biomarkers, Tumor / analysis*
  • Calcium-Binding Proteins
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology
  • Cohort Studies
  • DNA-Binding Proteins
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / biosynthesis*
  • Tumor Suppressor Proteins

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • DMBT1 protein, human
  • DNA-Binding Proteins
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins