Centrosome hyperamplification predicts progression and tumor recurrence in bladder cancer.

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.

• Authors: Yoshiaki Yamamoto, Hideyasu Matsuyama, Tomoko Furuya, Atsunori Oga, Satoru Yoshihiro, Masaru Okuda, Shigeto Kawauchi, Kohsuke Sasaki, Katsusuke Naito
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 19 Pg. 6449-55 (Oct 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15475431 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Aged
• Aged, 80 and over
• Aneuploidy
• Centrosome (metabolism)
• Chromosome Aberrations
• Chromosomes, Human, Pair 17 (genetics)
• Chromosomes, Human, Pair 20 (genetics)
• Chromosomes, Human, Pair 7 (genetics)
• Chromosomes, Human, Pair 9 (genetics)
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Prognosis
• Survival Analysis
• Urinary Bladder Neoplasms (genetics, metabolism, pathology)