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BJU Int. 2008 Jul;102(2):247-52. doi: 10.1111/j.1464-410X.2008.07572.x. Epub 2008 Jul 1.

Aurora kinase B is an independent protective factor in superficial bladder tumours with a dysfunctional G1 checkpoint.

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1
Department of Urology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

Abstract

OBJECTIVES:

To investigate the clinical role of Aurora kinases (essential for regulating mitosis) in human bladder pathogenesis, by quantifying Aurora kinase A and B, phospho-Aurora A, and phospho-Rb and p53 in bladder tumours, analysing the correlations between expression and clinicopathological features.

PATIENTS AND METHODS:

We evaluated levels of Aurora A, B, phospho-Aurora A, phospho-Rb and p53 in 73 superficial bladder tumours using tissue microarrays and immunohistochemistry, and correlated expression with pathological variables and clinical outcome.

RESULTS:

None of the Aurora proteins, when analysed alone, significantly predicted either tumour recurrence or progression. In tumours with an aberrant G1 checkpoint, assessed by phospho-Rb and p53 status, expression of neither Aurora A nor its phosphorylated form predicted either tumour recurrence or progression. Surprisingly, high expression of Aurora B in tumours with an aberrant G1 checkpoint significantly protected from tumour recurrence. On multivariate analysis, Aurora B was the only significant factor that predicted tumour recurrence in the presence of either phospho-Rb or mutated p53. This difference was not evident in tumours with an intact G1 checkpoint.

CONCLUSIONS:

High expression of Aurora B in superficial bladder tumours with an aberrant G1 checkpoint significantly protects patients from tumour recurrence. The potential application of nonspecific Aurora kinase inhibitors in non-muscle-invasive bladder cancer might be detrimental.

[Indexed for MEDLINE]
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