RESUMO
AIM: Overexpression of Aurora-A/STK15 kinase (hereafter AUKRA) is seen in a variety of epithelial cancers, such as gastrointestinal and gynaecological carcinomas. Its role as prognostic and/or predictive marker for adjuvant therapy of patients with advanced ovarian cancer is however still unclear. Therefore, the present study aimed at determining (1) the clinical value of AURKA expression (mRNA and protein) in 115 patients with ovarian carcinomas and (2) the basis of AURKA overexpression at the DNA level. METHODS: Formalin-fixed and Paraffin-embedded tissue samples (ovarian carcinoma: n=115; non-neoplastic ovaries: n=28) were processed for microdissection and quantitative RT-PCR as well as for semi-quantitative immunohistochemistry (IHC) of tissue microarrays according to standardised protocols. Fluorescence in Situ Hybridisation (FISH) was performed in a sub-set of cases (n=37) to analyse AURKA DNA copy numbers. RESULTS: The results demonstrate significantly elevated AURKA expression at the mRNA and protein level in ovarian carcinomas as compared to non-neoplastic ovaries (p < 0.0001). AURKA protein overexpression was observed in 68/107 (63.5%) of cases. For patients with stage III ovarian carcinoma having been optimally debulked and receiving adjuvant Taxane-based chemotherapy, AURKA overexpression was significantly linked to prolonged overall survival (p = 0.02). Finally AURKA overexpression was associated with increased AURKA DNA copy numbers (p = 0.01). CONCLUSION: In summary, AURKA overexpression, which is regulated at the DNA level, is a novel predictive marker for a subgroup of patients with stage III ovarian carcinomas.
