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

Purpose: To assess the prevalence and prognostic significance of Ki-ra s codon 12 mutations in extrahepatic biliary system cancer (EBSC). Pat ients and Methods: Patients diagnosed with EBSC between 1980 and 1990 (N = 111) were selected from two hospitals. DNA was amplified from par affin-embedded tissues and mutations in codon 12 of Ki-ras were detect ed 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 mu tations and clinical and pathologic characteristics; however, mutation s in Ki-ros were associated with survival, with a median survival dura tion of 7.7 months for patients with wild-type Ki-ras and 1.7 months f or patients with mutated tumors (hazards ratio [HR] = 1.67; P = .075), Among patients with stage I to II tumors, the chance of dying of pati ents with the mutation was 7.8 times higher than that of patients with out the mutation (P = .087); the corresponding HR for patients with st age III to IV disease was 2.9 (P = .003), After adjusting for age, tum or site, histology, differentiation, and stage, the HR for Ki-ras muta tions was 2.12 (P = .026). Conclusion: Ki-ras codon 12 mutations are a n independent prognostic indicator in patients with EBSC, Mutation det ection may be of help in the management of these patients. (C) 1995 by American Society of Clinical Oncology.