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Molecular Oncology, Markers, Clinical Correlates |
Departments of 1 Urology and 2 Pathology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan; and 3 Department of Veterinary Internal Medicine, Faculty of Agriculture, Yamaguchi University, Yoshida, Yamaguchi, Japan
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 (
pT1: 43; 
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 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.
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