title: Nerve Growth Factor Expression Is Not Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma.
abstract: BACKGROUND
  Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers.
  
  
  OBJECTIVE
  To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival.
  
  
  METHODS
  Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses.
  
  
  RESULTS
  High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival.
  
  
  CONCLUSIONS
  Intratumoral nerve growth factor expression is not associated with perineural invasion or recurrence-free and overall survival in patients with resected extrahepatic cholangiocarcinoma.
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. kazuhide-urabe@hiroshima-u.ac.jp.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Urabe
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. mura777@hiroshima-u.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. k-naru@par.odn.ne.jp.
authors.forename: Naru
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. umk@hiroshima-u.ac.jp.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. hashimoto@hiroshima-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. naoyaman423@gmail.com.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakagawa
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. hayato40013@gmail.com.
authors.forename: Hayato
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Natural Science Center for Basic Research and Development, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. eiso@hiroshima-u.ac.jp.
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. shiny@mte.biglobe.ne.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. sueda@hiroshima-u.ac.jp.
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D020932:Nerve Growth Factor / Q000378:metabolism*; D010525:Peripheral Nerves / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C502240:NGF protein, human; D020932:Nerve Growth Factor
keywords: Cholangiocarcinoma; Nerve growth factor; Perineural invasion; Survival