title: KRASMutation as a Potential Prognostic Biomarker of Biliary Tract Cancers.
abstract: BACKGROUND
  The aim of this study was to identify the unique molecular characteristics of biliary tract cancer (BTC) for the development of novel molecular-targeted therapies.
  
  
  METHODS
  We performed mutational analysis ofKRAS,BRAF,PIK3CA, andFBXW7and immunohistochemical analysis of EGFR and TP53 in 63 Japanese patients with BTC and retrospectively evaluated the association between the molecular characteristics and clinicopathological features of BTC.
  
  
  RESULTS
  KRASmutations were identified in 9 (14%) of the 63 BTC patients; no mutations were detected within the analyzed regions ofBRAF,PIK3CA, andFBXW7. EGFR overexpression was observed in 5 (8%) of the 63 tumors, while TP53 overexpression was observed in 48% (30/63) of the patients. Overall survival of patients withKRASmutation was significantly shorter than that of patients with the wild-typeKRASgene (P= 0.005). By multivariate analysis incorporating molecular and clinicopathological features,KRASmutations and lymph node metastasis were identified to be independently associated with shorter overall survival (KRAS,P= 0.004; lymph node metastasis,P= 0.015).
  
  
  CONCLUSIONS
  Our data suggest thatKRASmutation is a poor prognosis predictive biomarker for the survival in BTC patients.
authors.affiliation: Department of Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Laboratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: Department of Laboratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Ohtsuka
authors.affiliation: Department of Laboratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Matsushima
authors.affiliation: Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohkura
authors.affiliation: Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.affiliation: Department of Laboratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugiyama
keywords: KRAS; biliary tract cancer; biomarker; molecular targeted therapy