Expression of mitotic kinases phospho-aurora A and aurora B correlates with clinical and pathological parameters in bladder neoplasms

Abstract

Aurora A and Aurora B are serine-threonine kinase proteins which have both been implicated in human carcinogenesis through development of aneuploidy and chromosomal instability. The aim of the study is to assess the correlation of both markers with clinical and pathological parameters in patients with bladder cancer of different grade and stage. A bladder cancer cell line was assessed for Aurora A and Aurora B expression by Western blotting. Furthermore, 85 consecutive cases of bladder neoplasms obtained by transurethral resection were quantitatively and qualitatively analysed by immunohistochemistry for Phospho-Aurora A and Aurora B expression. All cases were stratified in 4 groups according to intracellular localization (nuclear, cytoplasmic) of both markers. The association between each group and clinical and pathological parameters was assessed by statistical analysis. Higher expression of cytoplasmic PhosphoAurora A correlated significantly with poor histological differentiation (G3 vs. G1) and advanced stage (p<0.05); there was also high significant correlation between nuclear Aurora B and both grading (both G3 and G2 vs. G1) and mitotic index (p<0.05). No statistically significant association was found between protein levels detected in tumour and sex or age (p>0.05). To our knowledge, the present study is the first to highlight the existence of a statistical association between such markers and traditional prognostic factors in bladder cancer. These findings indicate that Aurora A and B could be involved in the tumorigenesis of bladder cancer, thus providing a basis for a target therapy approach by using specific anti-mitotic agents.