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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aurora Kinase A
  • Aurora Kinase B
  • Aurora Kinases
  • Carcinoma, Transitional Cell / enzymology*
  • Carcinoma, Transitional Cell / pathology
  • Case-Control Studies
  • Disease Progression
  • Female
  • G1 Phase
  • Humans
  • Immunohistochemistry
  • Male
  • Microarray Analysis
  • Middle Aged
  • Neoplasm Recurrence, Local / enzymology*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Protein Serine-Threonine Kinases / metabolism*
  • Urinary Bladder Neoplasms / enzymology*
  • Urinary Bladder Neoplasms / pathology

Substances

  • AURKA protein, human
  • AURKB protein, human
  • Aurora Kinase A
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases