Aurora-B protein expression is linked to initial response to taxane-based first-line chemotherapy in stage III ovarian carcinoma.

ABSTRACT

AIMS: Aurora kinases are central to cell proliferation and considered to be prognostic/predictive markers and therapeutic targets for epithelial cancers. Here, the prognostic/predictive value of Aurora-B protein expression was evaluated in patients with serous, FIGO stage III ovarian carcinomas treated with taxane- or platinum-based first-line chemotherapy (1st-CTx). METHODS: Immunohistochemistry was performed on tissue microarrays, including 80 ovarian carcinomas and 18 non-neoplastic ovaries, previously characterised for Aurora-A protein expression. None or marginal (score 0+1), moderate (score 2) and strong (score 3) Aurora-B protein expression was correlated with clinico-pathological parameters as well as recurrence-free survival (RFS) and overall survival (OS). RESULTS: While non-neoplastic ovaries were negative for Aurora-B, almost all (79/80; 99%) ovarian carcinomas exhibited Aurora-B positive tumour cells, with score 1 in 41/80 (51%), score 2 in 23/80 (29%) and score 3 in 15/80 (19%) cases. Aurora-B and Aurora-A protein expression correlated significantly (p=0.002). In optimal debulked patients, Aurora-B protein expression was associated with RFS (p=0.011, n=53) and marginally with OS (p=0.460; n=53). Moreover, Aurora-B protein expression was predictive for RFS of optimal debulked patients with taxane-based (p=0.006; n=32), but not with platinum-based (p=0.720; n=20) 1st-CTx. Aurora-B protein expression was not linked to OS in optimal debulked patients with either of the two 1st-CTx. CONCLUSIONS: Aurora-B protein expression frequently occurs in serous, FIGO stage III ovarian carcinomas, making it a 'drugable' molecular target in the majority of ovarian carcinoma patients. Moreover, Aurora-B protein expression is predictive for initial response to taxane-based 1st-CTx in optimal debulked, late stage ovarian carcinoma patients.