Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse
Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse
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DOI：
10.1038/modpathol.3800564
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发表时间：
2006-05-01
期刊：
影响因子：
7.5
通讯作者：
Going, JJ
中科院分区：
文献类型：
--
作者：
Al-Mulla, F;Behbehani, AI;Going, JJ
大量早期结直肠癌患者因转移性疾病复发。通过原发性肿瘤的遗传特征来识别这些患者可能允许更知情的随访和定制的辅助治疗。使用基于中期的比较基因组杂交（CGH）分析了70例早期和大部分微卫星稳定的结直肠癌患者的原发性肿瘤，并使用基于微阵列的CGH在一个患者子集中独立确认了畸变。在70例癌症中，61例适合CGH，56例患者的随访数据可用。使用单变量、多变量和Kaplan-Meier生存曲线分析基因组畸变与患者生存的相关性。转移性原发性肿瘤比非转移性原发性肿瘤表现出更复杂的基因组畸变。多变量分析显示，染色体4p缺失是早期结直肠癌的独立预后因素（风险比，9.6; 95%CI，3.3-28; P = 0.0001）。染色体臂8 p和18 q的缺失对无病生存率有统计学显著的负面影响。此外，原发性肿瘤同时缺失4号和14号染色体的预后比缺失其中任何一条染色体的预后差（P < 0.0001）。早期结直肠癌患者原发性肿瘤的基因谱分析在确定可能复发转移性疾病的患者亚组方面具有重要价值。因此，原发性肿瘤的分子遗传学特征应被认为是这一疾病的特定阶段的患者的主流管理。
A substantial number of patients with early-stage colorectal cancer relapse from metastatic disease. Identification of these patients by genetic profiling of their primary tumours may allow more informed follow-up and tailored administration of adjuvant therapy. Primary tumours from 70 patients with early-stage and largely microsatellite-stable colorectal cancer were profiled using metaphase-based comparative genomic hybridization (CGH) and the aberrations confirmed independently in a subset of patients using microarray-based CGH. Of the 70 cancers, 61 were amenable to CGH, and follow-up data was available from 56 patients. Genomic aberrations were correlated with patients' survival using univariate, multivariate and Kaplan-Meier survival curves. Metastatic primary tumours exhibited more complex genomic aberrations than non-metastatic primary tumours. Loss of chromosome 4p was an independent prognostic factor in early-stage colorectal cancer using multivariate analysis (Hazard ratio, 9.6; 95% CI, 3.3-28; P = 0.0001). Loss of both chromosome arms 8p and 18q had a statistically significant negative effect on disease-free survival. Moreover, primary tumours with loss of both chromosomes 4 and 14q bestowed poorer prognosis than tumours with loss of any one of the two chromosomes (P < 0.0001). Genetic profiling of primary tumours of patients with early-stage colorectal cancer is of significant value in identifying the subset of patients who may relapse with metastatic disease. Accordingly, the molecular genetic features of primary tumours should be considered in the mainstream management of patients with this specific stage of the disease.