Centrosome hyperamplification predicts progression and tumor recurrence in bladder cancer.
OBJECTIVE
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.


METHODS
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.
Department of Urology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
Yoshiaki
Y
Yamamoto
Hideyasu
H
Matsuyama
Tomoko
T
Furuya
Atsunori
A
Oga
Satoru
S
Yoshihiro
Masaru
M
Okuda
Shigeto
S
Kawauchi
Kohsuke
K
Sasaki
Katsusuke
K
Naito
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D018385:Centrosome / Q000378:metabolism*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*