title: Prognostic significance of K-ras codon 12 mutation in patients with resected gallbladder cancer.
abstract: BACKGROUND
  Point mutation of K-ras is associated with carcinogenesis and overall survival in various cancers. We investigated the mutational spectrum of K-ras codon 12 in resected normal and gallbladder cancer tissue samples in a Northern Indian population and correlated it with different clinicopathological parameters.
  
  
  METHODS
  Gallbladder tissues from normal (n = 24) and cancer patients (n = 39) were analyzed for K-ras codon 12 mutation by restriction fragment length polymorphism. Statistical analysis was carried out using the χ(2) test or Fisher's exact test. Survival was estimated using the Kaplan-Meier method, and the difference between survival curves was analyzed by the log-rank test.
  
  
  RESULTS
  The frequency of K-ras mutation was significantly higher (p = 0.001) in gallbladder cancer tissue samples (16/39) compared to normal samples (1/24). Patients with K-ras mutation had a significantly decreased overall survival (p = 0.003), particularly for stage II (p = 0.021) and III (p = 0.009) cancers. No significant correlation was observed with any of the other clinicopathological factors studied.
  
  
  CONCLUSIONS
  Gallbladder cancer has a high frequency of K-ras codon 12 mutation with poorer outcomes in resected stage II and III disease. K-ras mutational analysis has important prognostic implications that need to be investigated further.
authors.affiliation: Department of Surgical Gastroenterology, King George's Medical University, Lucknow, India.
authors.forename: Hasan Raza
authors.initials: HR
authors.lastname: Kazmi
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chandra
authors.forename: Jaya
authors.initials: J
authors.lastname: Nigam
authors.forename: M
authors.initials: M
authors.lastname: Noushif
authors.forename: Devendra
authors.initials: D
authors.lastname: Parmar
authors.forename: Vishal
authors.initials: V
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000368:Aged; D002763:Cholecystectomy; D003062:Codon; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007194:India; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017354:Point Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins