Malats N, Porta M, Piñol J L, Corominas J M, Rifà J, Real F X
Departmetn of Epidemiology, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
J Clin Oncol. 1995 Jul;13(7):1679-86. doi: 10.1200/JCO.1995.13.7.1679.
To assess the prevalence and prognostic significance of Ki-ras codon 12 mutations in extrahepatic biliary system cancer (EBSC).
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.
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).
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.
评估肝外胆管系统癌（EBSC）中Ki-ras密码子12突变的发生率及其预后意义。
从两家医院选取1980年至1990年间诊断为EBSC的患者（N = 111）。从石蜡包埋组织中扩增DNA，并使用人工限制性片段长度多态性（RFLP）技术检测Ki-ras密码子12的突变。
68.5%的患者有可用组织。突变发生率为41%。突变与临床和病理特征之间无关联；然而，Ki-ras突变与生存相关，野生型Ki-ras患者的中位生存时间为7.7个月，肿瘤突变患者为1.7个月（风险比[HR]=1.67；P = 0.075）。在I至II期肿瘤患者中，发生突变的患者死亡几率比未发生突变的患者高7.8倍（P = 0.087）；III至IV期疾病患者的相应HR为2.9（P = 0.003）。在对年龄、肿瘤部位、组织学、分化程度和分期进行校正后，Ki-ras突变的HR为2.12（P = 0.026）。
Ki-ras密码子12突变是EBSC患者的独立预后指标。突变检测可能有助于这些患者的管理。
