KI-RAS MUTATIONS AS A PROGNOSTIC FACTOR IN EXTRAHEPATIC BILE SYSTEM CANCER

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 wets no association between mutations and clinical and pathologic characteristics; however, mutations in Ki-ros 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. (C) 1995 by American Society of Clinical Oncology.