title: Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer.
abstract: BACKGROUND
  Although recent reports indicate that K-ras mutation status is a biomarker that acts as a prognostic factor, only a few analyses of K-ras mutation subtypes have been published. In addition, there are no reports that analyze overall survival and prognostic factors according to K-ras mutation status and subtypes in only unresectable pancreatic cancer (PC) determined from tissues obtained by endoscopic ultrasound-guided fine-needle aspiration.
  
  
  METHODS
  We retrospectively analyzed 242 patients who were diagnosed as having unresectable PC with available histological diagnosis. Clinical data collected included sex, age, Eastern Cooperative Oncology Group performance status, carbohydrate antigen (CA) 19-9, primary tumor location, stage (local or metastatic) according to TNM staging, first-line chemotherapy, K-ras mutation status and subtypes (G12D, G12V, and G12R), and overall survival. We analyzed the negative prognostic factors for reduced overall survival in unresectable PC patients using these data.
  
  
  RESULTS
  From multivariate analysis, CA19-9 ≥1000 U/ml (hazard ratio [HR] 1.78, 95 % confidence interval [CI] 1.28-2.46, P < 0.01), metastatic stage (HR 2.26, 95 % CI 1.58-3.24, P < 0.01), and mutant-K-ras (HR 1.76, 95 % CI 1.03-3.01, P = 0.04) were negative prognostic factors, indicating a reduced survival. Among the patients who had K-ras mutation subtypes, CA19-9 ≥1000 U/ml (HR 1.65, 95 % CI 1.12-2.37, P < 0.01), metastatic stage (HR 2.12, 95 % CI 1.44-3.14, P < 0.01), and the presence of the G12D or G12R mutations (HR 1.60, 95 % CI 1.11-2.28) were negative prognostic factors for overall survival.
  
  
  CONCLUSIONS
  K-ras mutation status and subtypes may be associated with survival duration in pancreatic cancer patients.
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogura
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamao
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Mizuno
authors.forename: Susumu
authors.initials: S
authors.lastname: Hijioka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imaoka
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaki
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Niwa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tajika
authors.forename: Shinya
authors.initials: S
authors.lastname: Kondo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Vikram
authors.initials: V
authors.lastname: Bhatia
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.forename: Waki
authors.initials: W
authors.lastname: Hosoda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000145:classification / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins