Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: comprehensive immunohistochemical study using a tissue microarray

Br J Cancer. 2014 Sep 23;111(7):1363-72. doi: 10.1038/bjc.2014.415. Epub 2014 Jul 31.

Abstract

Background: Epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial-mesenchymal transition is proposed to occur in various developmental processes and cancer progression. 'Cadherin switch', a process in which cells shift to express different isoforms of the cadherin transmembrane protein and usually refers to a switch from the expression of E-cadherin to N-cadherin, is one aspect of EMT and can have a profound effect on tumour invasion/metastasis. The aim of this study was to investigate the clinicopathological significance of EMT-related proteins and cadherin switch in extrahepatic cholangiocarcinoma (EHCC).

Methods: We investigated the association between altered expression of 12 EMT-related proteins and clinical outcomes in patients with EHCC (n=117) using immunohistochemistry on tissue microarrays.

Results: Univariate and multivariate analyses revealed that, in addition to N classification (P=0.0420), the expression of E-cadherin (P=0.0208), N-cadherin (P=0.0038) and S100A4 (P=0.0157) was each an independent and a significant prognostic factor. We also demonstrated that cadherin switch was independently associated with poor prognosis (P=0.0143) in patients with EHCC.

Conclusions: These results may provide novel information for selection of patients with EHCC who require adjuvant therapy and strict surveillance.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Extrahepatic / metabolism*
  • Bile Ducts, Extrahepatic / pathology
  • Bile Ducts, Intrahepatic / metabolism*
  • Bile Ducts, Intrahepatic / pathology
  • Biomarkers, Tumor / metabolism*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Tissue Array Analysis

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins