Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma
Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma
复制标题
DOI：
10.1093/jnci/91.18.1574
复制
发表时间：
1999-09-15
影响因子：
10.3
通讯作者：
Jenkins, RB
中科院分区：
文献类型：
--
作者：
Sato, K;Qian, JQ;Jenkins, RB
背景：前列腺癌中常见8号染色体改变，包括8 p21 -22丢失和8 q24增加。我们研究这些改变是否与前列腺癌预后不良有关。研究方法：我们使用双探针荧光原位杂交和DNA探针8 p22（脂蛋白脂酶基因），着丝粒8（8 cen），8 q24（c-myc基因），以确定相应的拷贝数在144例高级别，晚期（III期）前列腺癌的肿瘤样本。考克斯模型用于前列腺癌全身进展或患者死亡的多变量分析。所有统计检验均为双侧检验。结果：我们将8 p22、8 cen和c-myc拷贝数分为正常、丢失和获得。c-myc相对于着丝粒拷贝数的额外增加（AI）类别（即，c-myc的过度表达和扩增）。8 p22的改变与系统性进展或患者死亡无统计学显著相关。c-myc的改变与系统进展（P = 0.024）和患者死亡（P = 0.039）相关; c-myc的AI显示最差的结局。我们还评估了以下六种模式的8 p22 - 8 cen-c-myc基因座异常组合模式的预后相关性：正常-正常-正常、丢失-任何8 cen-正常、丢失-获得-获得、获得-获得-获得、非丢失-任何8 cen-AI和丢失-任何8 cen-AI，其中任何8 cen是8号染色体着丝粒的正常、丢失或获得。与其他模式的患者相比，任何8 cen-AI模式丢失的患者具有更早的全身进展（P = 0.009）和更早的原因特异性死亡（P = 0.013）。多变量分析表明，任何8 cen-AI模式丢失是全身进展的独立危险因素（P
Background: Chromosome 8 alterations, including loss of 8p21-22 and gain of 8q24, are commonly observed in prostate carcinoma. We examined whether these alterations are associated with poor prognosis in prostate cancer. Methods: We used dual-probe fluorescence in situ hybridization and DNA probes for 8p22 (lipoprotein lipase gene), centromere 8 (8cen), and 8q24 (c-myc gene) to determine the corresponding copy numbers in tumor samples from 144 patients with high-grade, advanced (stage III) prostate carcinoma. Cox models were used for multivariate analysis of systemic progression or patient death from prostate cancer. All statistical tests are two-sided. Results: We classified the 8p22, 8cen, and c-myc copy number as normal, loss, and gain. An additional increase (AI) category of c-myc relative to the centromere copy number (i.e., overrepresentation and amplification of c-myc) was also used. Alterations of 8p22 were not statistically significantly associated with either systemic progression or patient death. Alterations of c-myc were associated with both systemic progression (P =.024) and patient death (P =.039); AI of c-myc showed the poorest outcome. We also evaluated the prognostic relevance of the combined 8p22-8cen-c-myc loci anomaly pattern for the following six patterns: normal-normal-normal, loss-any 8cen-normal, loss-gain-gain, gain-gain-gain, non-loss-any 8cen-AI, and loss-any 8cen-AI, where any 8cen is normal, loss, or gain of the chromosome 8 centromere. Patients with the loss-any 8cen-AI pattern had earlier systemic progression (P =.009) and earlier cause-specific death (P =.013) than did patients with other patterns, Multivariate analyses demonstrated that the loss-any 8cen-AI pattern was an independent risk factor for systemic progression (P