Ki-ras mutations as a prognostic factor in extrahepatic bile system cancer. PANK-ras I Project Investigators

J Clin Oncol. 1995 Jul;13(7):1679-86. doi: 10.1200/JCO.1995.13.7.1679.

Abstract

Purpose: To assess the prevalence and prognostic significance of Ki-ras codon 12 mutations in extrahepatic biliary system cancer (EBSC).

Patients and methods: Patients diagnosed with EBSC between 1980 and 1990 (N = 111) were selected from two hospitals. DNA was amplified from paraffin-embedded tissues and mutations in codon 12 of Ki-ras were detected using the artificial restriction fragment-length polymorphism (RFLP) technique.

Results: Tissue was available from 68.5% of patients. The prevalence of mutations was 41%. There was no association between mutations and clinical and pathologic characteristics; however, mutations in Ki-ras were associated with survival, with a median survival duration of 7.7 months for patients with wild-type Ki-ras and 1.7 months for patients with mutated tumors (hazards ratio [HR] = 1.67; P = .075). Among patients with stage I to II tumors, the chance of dying of patients with the mutation was 7.8 times higher than that of patients without the mutation (P = .087); the corresponding HR for patients with stage III to IV disease was 2.9 (P = .003). After adjusting for age, tumor site, histology, differentiation, and stage, the HR for Ki-ras mutations was 2.12 (P = .026).

Conclusion: Ki-ras codon 12 mutations are an independent prognostic indicator in patients with EBSC. Mutation detection may be of help in the management of these patients.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Ampulla of Vater*
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Extrahepatic*
  • Codon / genetics*
  • Common Bile Duct Neoplasms / genetics*
  • Common Bile Duct Neoplasms / mortality
  • Common Bile Duct Neoplasms / pathology
  • Female
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / mortality
  • Gallbladder Neoplasms / pathology
  • Genes, ras / genetics*
  • Humans
  • Male
  • Middle Aged
  • Point Mutation / genetics*
  • Prevalence
  • Prognosis

Substances

  • Codon