Wadler S, Bajaj R, Neuberg D, Agarwal V, Haynes H, Benson A B
Albert Einstein College of Medicine, Bronx, New York, USA.
Cancer J Sci Am. 1997 Sep-Oct;3(5):284-8.
Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colorectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colorectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival.
Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-alpha or IFN-beta. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61.
Seventy-two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations.
It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.
c-Ki-ras2（ras）基因突变发生在约40%的结直肠癌患者中，且在该疾病发病机制的早期阶段出现。为评估ras基因突变的预后价值，东部肿瘤协作组（ECOG）开展了一项回顾性研究（EST 2292），以确定晚期结直肠癌患者中ras基因突变的频率，并确定ras基因突变是否与治疗反应改变及生存情况相关。
患者来自四项研究：P-Z289，一项ECOG关于晚期结直肠癌患者使用5-氟尿嘧啶（5-FU）和干扰素（IFN）的II期试验；P-Z991，一项ECOG关于晚期恶性肿瘤患者使用5-FU和IFN的I期试验；以及阿尔伯特爱因斯坦医学院的两项试验，试验对象为接受5-FU联合IFN-α或IFN-β治疗的晚期结直肠癌患者。所有患者均患有晚期结直肠癌，且有足够的组织学材料可用于分析ras的存在情况及类型，采用聚合酶链反应和斑点杂交分析，使用足以检测ras基因第12、13和61密码子所有常见突变的探针组。
72例患者入组本试验。检测到25例（35%）存在ras基因突变，其中第12密码子突变17例（23%），第13密码子突变4例（6%），第61密码子突变4例（6%）。ras基因突变的存在与年龄、性别、Dukes分期、组织学类型或肿瘤标志物之间无相关性。72例患者中有31例（43%）对5-FU和IFN治疗有反应，31例有反应者中有10例（32%）以及41例无反应者中有15例（37%）存在ras基因突变。有ras基因突变组和无ras基因突变组之间在反应率或总生存方面无差异。
对于接受5-FU和IFN治疗的结直肠癌患者，ras基因突变对治疗反应或生存情况不太可能具有显著的预后价值。
