Background: Centrosome is an organelle which forms bipolar spindle pole, and its replication is strictly regulated during cell cycle. Recently, centrosome amplification, defined as three or more centrosomes per cell, has been reported to occur frequently in a variety of malignancies. We investigated the role of centrosome amplification for the prognosis of bladder cancer patients. Materials and Methods: Eight established bladder cancer cell lines were studied to clarify the relation among centrosome amplification, genomic alterations, and cell cycle-related proteins. Additionally, 102 specimens from bladder cancer patients were studied for the clinical significance of centrosome amplification in bladder cancer. To detect centrosome amplification, genomic alterations, and cell cycle-related proteins, immunofluorecent staining using anti-pericentrin antibody, comparative genomic hybridization (CGH) or fluorescence in situ hybridization (FISH) , and immunohistchemical staining were applied, respectively. Results: Basic studies from established cell lines demonstrated that centrosome amplification was defied as cases with more than 5% fraction of cells with three or more centrosomes per cell, and that the centrosome amplification was significantly associated with overexpression of aurora-A kinase protein as well as the copy number gain of its gene loci (20q13. 2) , alterations of chromosome copy number including 7, 9, and 17, and several cell cycle-related proteins including p53, BubR1. Clinical investigations demonstrated the centrosome amplification occurred in 59 cases (57. 8%) , and proved to be an independent prognostic factors for tumor progression (Risk ratio: 3. 12, 95% CI: 1. 36-13. 4, p=0. 0039) for bladder cancer. Conclusion: Centrosome amplification seems to occur through the genetic mechanisms of p53 alterations, or aurora-A overexpression by chromosomal gain of 20q23. 2, and become a potential prognostic marker for the tumor progression in bladder cancer.
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