Dyskerin expression in human fetal, adult and neoplastic intrahepatic bile ducts: correlations with cholangiocarcinoma aggressiveness

Histopathology. 2015 Jan;66(2):244-51. doi: 10.1111/his.12480. Epub 2014 Nov 13.

Abstract

Aims: To investigate the immunohistochemical expression of dyskerin, a biomarker involved in ribosome production and telomere maintenance, in human fetal, adult and neoplastic bile ducts, and possible correlations with cholangiocarcinoma aggressiveness.

Methods and results: Sixty consecutive intrahepatic cholangiocarcinomas were collected and used for tissue microarray construction (total: 176 cores); clinical data and follow-up were also collected. Five fetal and 10 normal adult livers were included as controls. Automated immunohistochemistry for dyskerin, p53, and Ki67, and nucleolar silver staining, were performed. In normal livers, dyskerin expression was negative in smaller bile ducts (mean 44.8 μm) and positive in bile ducts of larger diameter (mean 116.1 μm; P < 0.001). Expression was positive in 56.7% of cholangiocarcinomas, and correlated with p53 mutation (P = 0.008) and a higher proliferative (Ki67) index (P = 0.003), which were included as markers of tumour aggressiveness. Finally, dyskerin-positive cholangiocarcinomas showed a negative trend in disease-free survival (P = 0.078) on univariate analysis.

Conclusions: The non-neoplastic biliary tree seems to progressively lose dyskerin expression from the major branches to the peripheral portal bile ducts. Similarly, intrahepatic cholangiocarcinomas showed two patterns of dyskerin expression, and the dyskerin-positive phenotype seemed to characterize more aggressive cholangiocarcinomas.

Keywords: biliary tree; cholangiocarcinoma; dyskerin; histopathology; immunohistochemistry.

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / embryology
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology*
  • Biomarkers, Tumor / analysis*
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / biosynthesis*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology*
  • Disease-Free Survival
  • Female
  • Fetus
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nuclear Proteins / analysis
  • Nuclear Proteins / biosynthesis*
  • Proportional Hazards Models
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • DKC1 protein, human
  • Nuclear Proteins