Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients

• Published in: Clinical cancer research 2007-07, Vol.13 (14), p.4098-4104
• Main Authors: LANDEN, Charles N, LIN, Yvonne G, IMMANENI, Anand, DEAVERS, Michael T, MERRITT, William M, SPANNUTH, Whitney A, BODURKA, Diane C, GERSHENSON, David M, BRINKLEY, William R, SOOD, Anil K
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Aurora Kinases; Aurora-A kinase; Biological and medical sciences; Cell Line, Tumor; centrosome; Centrosome - enzymology; Centrosome - pathology; clinical correlation; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Medical sciences; Middle Aged; Neoplasm Staging; ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Pharmacology. Drug treatments; Prognosis; Protein-Serine-Threonine Kinases - genetics; Survival Analysis; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-0431

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 by retrospective 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 by a substantial proportion of ovarian cancers and is associated with centrosome amplification and poor survival. It may be a useful prognostic marker and target in ovarian cancer.