Halling K C, French A J, McDonnell S K, Burgart L J, Schaid D J, Peterson B J, Moon-Tasson L, Mahoney M R, Sargent D J, O'Connell M J, Witzig T E, Farr G H, Goldberg R M, Thibodeau S N
Departments of Laboratory Medicine and Pathology, Mayo Foundation, Rochester, MN 55905, USA.
J Natl Cancer Inst. 1999 Aug 4;91(15):1295-303. doi: 10.1093/jnci/91.15.1295.
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.
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.
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 [HR] = 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).
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.
微卫星不稳定性（MSI）以及涉及5号染色体长臂、8号染色体短臂、17号染色体短臂和18号染色体长臂的等位基因失衡是在结直肠癌中常见的基因改变。我们研究了这些基因改变的存在与否是否能将阿斯泰勒-科勒B2期或C期结直肠癌患者分层为预后良好和不良的组。
使用位于5号染色体长臂、8号染色体短臂、15号染色体长臂、17号染色体短臂和18号染色体长臂上的11个微卫星标记，对508例患者的肿瘤进行MSI和等位基因失衡评估。检查涉及每个这些标记的基因改变与生存和疾病复发的相关性。所有P值均为双侧。
在单变量分析中，高微卫星不稳定性（MSI-H），即在所检测位点的30%或更多位点存在MSI，与生存率提高（P = 0.02）和复发时间延长（P = 0.01）相关。肿瘤在8号染色体短臂表现出等位基因失衡的患者组生存率降低（P = 0.02）和复发时间缩短（P = 0.004）。在5号染色体长臂、15号染色体长臂、17号染色体短臂或18号染色体长臂上的标记与生存或复发时间未观察到统计学上的显著相关性。在多变量分析中，MSI-H是生存率提高（风险比[HR] = 0.51；95%置信区间[CI] = 0.31 - 0.82；P = 0.006）和复发时间延长（HR = 0.42；95% CI = 0.24 - 0.74；P = 0.003）的独立预测因素，8号染色体短臂等位基因失衡是生存率降低（HR = 1.89；95% CI = 1.25 - 2.8；P = 0.002）和复发时间缩短（HR = 2.07；95% CI = 1.32 - 3.25；P = 0.002）的独立预测因素。
肿瘤表现出MSI-H的患者预后良好，而具有8号染色体短臂等位基因失衡的患者预后不良；这两种改变均为独立的预后因素。据我们所知，这是关于8号染色体短臂等位基因失衡与结直肠癌患者生存之间关联的首次报告。
