title: Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: comprehensive immunohistochemical study using a tissue microarray.
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.
authors: 1] Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan [2] Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: T
authors: T
authors: Nitta
authors: Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: T
authors: T
authors: Mitsuhashi
authors: Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: Y
authors: Y
authors: Hatanaka
authors: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: M
authors: M
authors: Miyamoto
authors: Translational Research and Clinical Trial Center, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: K
authors: K
authors: Oba
authors: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: T
authors: T
authors: Tsuchikawa
authors: Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: Y
authors: Y
authors: Suzuki
authors: Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: K C
authors: KC
authors: Hatanaka
authors: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: S
authors: S
authors: Hirano
authors: Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan.
authors: Y
authors: Y
authors: Matsuno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins