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


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.
Bruyere
Franck
F
Department of Urology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Corcoran
Niall M
NM
Berdjis
Navid
N
Namdarian
Benjamin
B
Pedersen
John
J
Ockrim
Jeremy
J
Voelzke
Bryan B
BB
Costello
Anthony J
AJ
Hovens
Christopher M
CM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D016193:G1 Phase; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology
C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases