Molecular predictors of survival after adjuvant chemotherapy for colon cancer.
Molecular predictors of survival after adjuvant chemotherapy for colon cancer.
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DOI：
10.1056/nejm200104193441603
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发表时间：
2001-04-19
影响因子：
158.5
通讯作者：
Hamilton, SR
中科院分区：
文献类型：
--
作者：
Watanabe, T;Wu, T;Hamilton, SR
背景资料：辅助化疗提高了III期结肠癌患者的生存率，但没有可靠的分子预测的结果已经identified.Methods：我们评估了染色体材料的损失（也称为杂合性或等位基因丢失）从染色体18 q，17 p和8 p;细胞水平的p53和p21（WAF 1/CIP 1）蛋白;和微卫星不稳定性作为分子标记。我们分析了460例III期和高风险II期结肠癌患者的肿瘤组织，这些患者接受了辅助氟尿嘧啶、亚叶酸和左旋咪唑的各种组合治疗，以确定这些标记物预测生存率的能力。结果：319例癌症中有155例（49%）存在18 q杂合性缺失。在298个肿瘤中的62个（21%）中发现了高水平的微卫星不稳定性，并且这62个肿瘤中的38个（61%）具有转化生长因子β 1（TGF-β 1）II型受体基因的突变。在微卫星稳定的III期癌症患者中，氟尿嘧啶化疗后的5年总生存率在癌症保留18 q等位基因的患者中为74%，在18 q等位基因缺失的患者中为50%（18 q缺失的死亡相对风险为2.75; 95%置信区间为1.34至5.65; P = 0.006）。在肿瘤具有高水平微卫星不稳定性的患者中，存在TGF-β 1 II型受体突变基因的患者的五年生存率为74%，而如果肿瘤没有这种突变，则为46（死亡的相对危险度为2.90; 95%可信区间为1.14 ~ 7.35; P = 0.03）。微卫星稳定性癌症中18 q等位基因的保留和TGF-β II型受体基因的突变在具有高水平微卫星不稳定性的癌症中，β 1的表达表明III期结肠癌患者在以氟尿嘧啶为基础的方案进行辅助化疗后的良好结局。（N Engl J Med 2001;344：1196-206.）版权所有（C）2001马萨诸塞州医学会。
Background: Adjuvant chemotherapy improves survival among patients with stage III colon cancer, but no reliable molecular predictors of outcome have been identified.Methods: We evaluated loss of chromosomal material (also called loss of heterozygosity or allelic loss) from chromosomes 18q, 17p, and 8p; cellular levels of p53 and p21(WAF1/CIP1) proteins; and microsatellite instability as molecular markers. We analyzed tumor tissue from 460 patients with stage III and high-risk stage II colon cancer who had been treated with various combinations of adjuvant fluorouracil, leucovorin, and levamisole to determine the ability of these markers to predict survival.Results: Loss of heterozygosity at 18q was present in 155 of 319 cancers (49 percent). High levels of microsatellite instability were found in 62 of 298 tumors (21 percent), and 38 of these 62 tumors (61 percent) had a mutation of the gene for the type II receptor for transforming growth factor beta1 (TGF-beta1). Among patients with microsatellite-stable stage III cancer, five-year overall survival after fluorouracil-based chemotherapy was 74 percent in those whose cancer retained 18q alleles and 50 percent in those with loss of 18q alleles (relative risk of death with loss at 18q, 2.75; 95 percent confidence interval, 1.34 to 5.65; P = 0.006). The five-year survival rate among patients whose cancer had high levels of microsatellite instability was 74 percent in the presence of a mutated gene for the type II receptor for TGF-beta1 and 46 percent if the tumor did not have this mutation (relative risk of death, 2.90; 95 percent confidence interval, 1.14 to 7.35; P = 0.03).Conclusions: Retention of 18q alleles in microsatellite-stable cancers and mutation of the gene for the type II receptor for TGF-beta1 in cancers with high levels of microsatellite instability point to a favorable outcome after adjuvant chemotherapy with fluorouracil-based regimens for stage III colon cancer. (N Engl J Med 2001;344:1196-206.) Copyright (C) 2001 Massachusetts Medical Society.