Centrosome hyperamplification predicts progression and tumor recurrence in bladder cancer
Centrosome hyperamplification predicts progression and tumor recurrence in bladder cancer
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DOI：
10.1158/1078-0432.ccr-04-0773
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发表时间：
2004-10-01
影响因子：
11.5
通讯作者：
Naito, K
中科院分区：
文献类型：
--
作者：
Yamamoto, Y;Matsuyama, H;Naito, K
目的：最近的研究表明，中心体高扩增与膀胱癌的染色体不稳定密切相关。在这项研究中，我们探讨了CH是否可以作为膀胱癌患者的预后生物标志物。实验设计：用免疫组织化学方法对50例膀胱癌(TopT1：43；大于或等于topT2：7)的CH进行评估。此外，用荧光原位杂交技术检测了Aurora-A基因所在的7、9、17号染色体的数量畸变率和20q13的获得率，并对DNA倍性进行了评估。对8个膀胱癌细胞株的初步实验发现，有6个细胞株的CH细胞数超过5%，并伴随20q13的增加和Aurora-A的过度表达；因此，CH阳性病例(CH+)被定义为每个细胞具有大于或等于3个中心体数的5%以上的细胞。结果：在30例(60%)、18例(36%)、22例(44%)和19例(38%)的患者中，分别检测到CH+、20q13增加、染色体不稳定和DNA异倍体。CH+组和CH-组在肿瘤数目、分级、复发和进展方面有显著差异。后者的无复发和无进展生存率显著高于前者(分别为P=0.0028和P=0.0070，对数等级检验)。多因素分析显示CH+是预测非肌肉浸润性膀胱癌复发的最重要因素(风险比为1.882；95%可信区间为1.161~3.325；P=0.0094)。结论：检测CH可为预测膀胱癌复发提供重要的预后信息。
Purpose: Recent studies have reported that centrosome hyperamplification (CH) is closely related to chromosomal instability in bladder cancer. In this study, we investigated whether CH could be used as a prognostic biomarker for patients with bladder cancer.Experimental Design: CH was evaluated by immunohistochemistry in 50 bladder cancers (less than or equal topT1: 43; greater than or equal topT2: 7). In addition, numerical aberrations of chromosomes 7, 9, and 17 and gain of 20q13, on which the Aurora-A gene is located, were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed. Preliminary experiments on eight bladder cancer cell lines found that six had over 5% of CH cells associated with a gain of 20q13 and overexpression of Aurora-A; therefore, CH-positive cases (CH+) were defined as those having over 5% of cells with greater than or equal to3 centrosomes per cell.Results: CH+, 20q13 gain, chromosomal instability, and DNA aneuploidy were detected in 30 (60%), 18 (36%), 22 (44%), and 19 (38%) patients, respectively. There were significant differences in tumor number, grade, recurrence, and progression between the CH+ and CH- groups. The later had significantly higher recurrence-free and progression-free survivals than the former (P = 0.0028 and P = 0.0070, respectively, log-rank test). Multivariate analysis revealed that CH+ was the strongest predictor for tumor recurrence in nonmuscle invasive (pTa and pT1) bladder cancer (hazard ratio, 1.882; 95% confidence interval, 1.161-3.325; P = 0.0094).Conclusions: Detection of CH may provide crucial prognostic information about tumor recurrence in bladder cancer.