title: Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma.
abstract: BACKGROUND
  Cholangiocarcinoma (CC) is a highly malignant carcinoma. We attempted to clarify the prognostic significance of c-Met overexpression and its association with clinicopathological factors in patients with CC.
  
  
  METHODS
  One hundred and eleven patients with intrahepatic CC (IHCC) and 136 patients with extrahepatic CC (EHCC) who had undergone curative surgery were divided immunohistologically into c-Met(high) and c-Met(low) groups. Clinicopathological factors and outcomes were compared between the groups. c-Met and epidermal growth factor receptor (EGFR) expression was also examined in 10 CC cell lines.
  
  
  RESULTS
  The positivity of c-Met was 45.0% in IHCC and 68.4% in EHCC; c-Met(high) expression was demonstrated in 11.7% of IHCC and 16.2% of EHCC. c-Met(high) expression was significantly correlated with the 5-year survival rate for CC overall (P=0.0046) and for IHCC (P=0.0013), histopathological classification in EHCC, and for EGFR overexpression in both IHCC and EHCC. Coexpression and coactivation of c-Met and EGFR were also observed in CC cell lines. Multivariate analysis revealed that c-Met(high) expression was an independent predictor of poor overall and disease-free survival in patients with IHCC.
  
  
  CONCLUSIONS
  c-Met overexpression is associated with EGFR expression and is a poor prognostic factor in CC.
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Ojima
authors.forename: M
authors.initials: M
authors.lastname: Iwasaki
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: A
authors.initials: A
authors.lastname: Kokubu
authors.forename: N
authors.initials: N
authors.lastname: Hiraoka
authors.forename: T
authors.initials: T
authors.lastname: Kosuge
authors.forename: D
authors.initials: D
authors.lastname: Yoshikawa
authors.forename: T
authors.initials: T
authors.lastname: Kono
authors.forename: H
authors.initials: H
authors.lastname: Furukawa
authors.forename: T
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015996:Survival Rate
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met