Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers
Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers
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DOI：
10.1158/0008-5472.can-05-0404
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发表时间：
2005-07-15
期刊：
影响因子：
11.2
通讯作者：
Slattery, ML
中科院分区：
文献类型：
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作者：
Samowitz, WS;Sweeney, C;Slattery, ML
BRAF V600 E突变与结肠癌中的微卫星不稳定性和CpG岛甲基化表型（CIMP）相关。我们评估了一个大的人群为基础的样本与结肠癌的个人，以确定其与生存和其他临床病理变量的关系。V600 E BRAF突变见于5%（40/803）的微卫星稳定肿瘤和51.8%（43/83）的微卫星不稳定肿瘤。在微卫星稳定的肿瘤中，该突变与生存率低、CIMP高、美国癌症联合委员会（AJCC）分期晚期和结直肠癌家族史相关[比值比，4.23; 95%置信区间（95%CI），1.65-10.84]。5年生存率单因素分析显示，（16.7%对60.0%; P < 0.01）;在校正了年龄、分期和肿瘤部位的分析中[风险率比（HRR），2.97; 95% CI，2.05-4.32];在AJCC 2 - 4期的分期特异性、年龄校正分析中（HRR分别为4.88、3.60和2.04）;在AJCC 2 - 4期的Kaplan-Meier生存估计中（所有三个分期P < 0.01）。无论V600 E突变存在与否，微卫星不稳定肿瘤均与良好的5年生存率相关（分别为76.2%和75.0%）。我们的结论是，微卫星稳定的结肠癌中BRAF V600 E突变与2 - 4期结肠癌的生存率显著降低相关，但对微卫星不稳定肿瘤的良好预后没有影响。
The BRAF V600E mutation has been associated with micro-satellite instability and the CpG island methylator phenotype (CIMP) in colon cancer. We evaluated a large population-based sample of individuals with colon cancer to determine its relationship to survival and other clinicopathologic variables. The V600E BRAF mutation was seen in 5% (40 of 803) of microsatellite-stable tumors and 51.8% (43 of 83) of microsatellite-unstable tumors. In microsatellite-stable tumors, this mutation was related to poor survival, CIMP high, advanced American joint Committee on Cancer (AJCC) stage, and family history of colorectal cancer [odds ratio, 4.23; 95% confidence interval (95% CI), 1.65-10.84]. The poor survival was observed in a univariate analysis of 5-year survival (16.7% versus 60.0%; P < 0.01); in an analysis adjusted for age, stage, and tumor site [hazard rate ratio (HRR), 2.97; 95% CI, 2.05-4.32]; in stage-specific, age-adjusted analyses for AJCC stages 2 to 4 (HRR, 4.88, 3.60, and 2.04, respectively); and in Kaplan-Meier survival estimates for AJCC stages 2 to 4 (P < 0.01 for all three stages). Microsatellite-unstable tumors were associated with an excellent 5-year survival whether the V600E mutation was present or absent (76.2% and 75.0%, respectively). We conclude that the BRAF V600E mutation in microsatellite - stable colon cancer is associated with a significantly poorer survival in stages 2 to 4 colon cancer but has no effect on the excellent prognosis of microsatellite-unstable tumors.