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

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.