Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers
Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers
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DOI：
10.1093/jnci/91.15.1295
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发表时间：
1999-08-04
影响因子：
10.3
通讯作者：
Thibodeau, SN
中科院分区：
文献类型：
--
作者：
Halling, KC;French, AJ;Thibodeau, SN
背景：涉及染色体臂5q、8p、17p和18q的微卫星不稳定性和等位基因失衡是结直肠癌中常见的遗传改变。我们研究了是否存在或不存在这些基因改变将Astler-Coller期B2或C期结直肠癌患者分层为预后有利和不利组。方法：利用位于染色体臂5q、8p、15q、17p和18q上的11个微卫星标记，对508例肿瘤患者的MSI和等位基因失衡进行评估，检测涉及这些标记的遗传改变与生存和疾病复发的关系。所有P值都是双面的。结果:在单因素分析中，高MSI (MSI- h)，即30%或更多的检测位点的MSI，与生存率的提高（P = 0.02）和复发时间（P = 0.01）相关，肿瘤在染色体8p上表现出等位基因失衡的患者组生存率降低（P = 0.02）和复发时间（P = 0.004），在染色体臂5q， 15q, 17p，或18q上的标记与生存率或复发时间没有统计学意义上的显著相关性。MSI-H是改善生存率（危险比[HP] = 0.51； 95%可信区间[CI] = 0.31-0.82; P = 0.006）和复发时间（HR = 0.42; 95% CI = 0.24-0.74; P = 0.003）的独立预测因子，8p等位基因失衡是降低生存率（HR = 1.89; 95% CI = 1.25-2.83; P = 0.002）和复发时间(HR = 2.07; 95% CI = 1.32-3.25；P = 0.002)。结论：MSI-H患者预后良好，8p等位基因失衡患者预后较差；这两种改变都是独立的预后因素。据我们所知，这是首次报道8p等位基因失衡与结直肠癌患者生存之间的关系。
Background: Microsatellite instability (MSI) and allelic imbalance involving chromosome arms 5q, 8p, 17p, and 18q are genetic alterations commonly found in colorectal cancer. We investigated whether the presence or absence of these genetic alterations would allow stratification of patients with Astler-Coller stage B2 or C colorectal cancer into favorable and unfavorable prognostic groups. Methods: Tumors from 508 patients were evaluated for MSI and allelic imbalance by use of 11 microsatellite markers located on chromosome arms 5q, 8p, 15q, 17p, and 18q, Genetic alterations involving each of these markers were examined for associations with survival and disease recurrence. All P values are two-sided. Results: In univariate analyses, high MSI (MSI-H), i.e., MSI at 30% or more of the loci examined, was associated with improved survival (P = .02) and time to recurrence (P = .01), The group of patients whose tumors exhibited allelic imbalance at chromosome 8p had decreased survival (P = .02) and time to recurrence (P = .004), No statistically significant associations with survival or time to recurrence were observed for markers on chromosome arms 5q, 15q, 17p,Or 18q, In multivariate analyses, MSI-H was an independent predictor of improved survival (hazard ratio [HP] = 0.51; 95% confidence interval [CI] = 0.31-0.82; P = .006) and time to recurrence (HR = 0.42; 95% CI = 0.24-0.74; P = .003), and 8p allelic imbalance was an independent predictor of decreased survival (HR = 1.89; 95% CI = 1.25-2.83; P = .002) and time to recurrence (HR = 2.07; 95% CI = 1.32-3.25; P = .002), Conclusions: Patients whose tumors exhibited MSI-H had a favorable prognosis, whereas those with 8p allelic imbalance had a poor prognosis; both alterations served as independent prognostic factors, To our knowledge, this is the first report of an association between 8p allelic imbalance and survival in patients with colorectal cancer.