Overexpression of the centrosomal protein Aurora-A kinase is associated with poor prognosis in epithelial ovarian cancer patients

Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma. Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian cancers), and clinical variables were collected byr etrospective chart review. Centrosome amplification was assessed by immunofluorescence in cell lines, and by immunohistochemistry in patient samples. Results: All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase expression was strongly associated with supernumerary centrosome count in tumor cells (P < 0.001). Tumors with the greatest Aurora-A overexpression (n = 24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P = 0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival (P < 0.05) by multivariate analysis. Conclusions: Aurora-A kinase is overexpressed bya substantial proportion of ovarian cancers and is associated with centrosome amplification and poor survival. It maybe a useful prognostic marker and target in ovarian cancer.