title: Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?
abstract: OBJECTIVE
  To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer.
  
  
  METHODS
  Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model.
  
  
  RESULTS
  On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(-), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasis-free survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained (p = 0.2940). Tumor location was the only independent prognostic factor predicting OS (p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS (p = 0.0030, 0.0013, and 0.0037, respectively).
  
  
  CONCLUSIONS
  This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients.
authors.affiliation: Department of Radiation Oncology, Hanyang University Hospital, Seoul, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. kyubokim@snu.ac.kr.
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Paik
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.|Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
authors.forename: E K
authors.initials: EK
authors.lastname: Chie
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: S-W
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: D-Y
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: S-A
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: T-Y
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Bang
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.|Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Ha
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D017734:Bile Ducts, Extrahepatic / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D059186:Chemoradiotherapy, Adjuvant; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Adjuvant chemoradiotherapy; Extrahepatic bile duct cancer; c-Met