中心体过度扩增可预测膀胱癌的进展和肿瘤复发。

Centrosome hyperamplification predicts progression and tumor recurrence in bladder cancer.

作者信息

Yamamoto Yoshiaki, Matsuyama Hideyasu, Furuya Tomoko, Oga Atsunori, Yoshihiro Satoru, Okuda Masaru, Kawauchi Shigeto, Sasaki Kohsuke, Naito Katsusuke

机构信息

Department of Urology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.

出版信息

Clin Cancer Res. 2004 Oct 1;10(19):6449-55. doi: 10.1158/1078-0432.CCR-04-0773.

DOI:10.1158/1078-0432.CCR-04-0773

PMID:15475431

Abstract

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 (< or =pT1: 43; > or =pT2: 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 > or =3 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.

摘要

目的

近期研究报道，中心体过度扩增（CH）与膀胱癌的染色体不稳定性密切相关。在本研究中，我们调查了CH是否可作为膀胱癌患者的预后生物标志物。

实验设计

通过免疫组织化学对50例膀胱癌（≤pT1：43例；≥pT2：7例）进行CH评估。此外，通过荧光原位杂交评估7号、9号和17号染色体的数目畸变以及位于20q13上的Aurora-A基因的扩增情况，并评估DNA倍体。对8种膀胱癌细胞系进行的初步实验发现，其中6种细胞系中CH细胞超过5%，伴有20q13扩增和Aurora-A过表达；因此，CH阳性病例（CH+）定义为每个细胞中具有≥3个中心体的细胞超过5%的病例。

结果

分别在30例（60%）、18例（36%）、22例（44%）和19例（38%）患者中检测到CH+、20q13扩增、染色体不稳定性和DNA非整倍体。CH+组和CH-组在肿瘤数量、分级、复发和进展方面存在显著差异。CH-组的无复发生存率和无进展生存率显著高于CH+组（对数秩检验，P值分别为0.0028和0.0070）。多变量分析显示，CH+是非肌层浸润性（pTa和pT1）膀胱癌肿瘤复发的最强预测因子（风险比，1.882；95%置信区间，1.161 - 3.325；P = 0.0094）。