This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Landen, C. N. Articles by Sood, A. K. Search for Related Content PubMed PubMed Citation Articles by Landen, C. N., Jr. Articles by Sood, A. K.

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

Authors' Affiliations: Departments of ¹ Gynecologic Oncology, ² Pathology, and ³ Cancer Biology, University of Texas M. D. Anderson Cancer Center, and ⁴ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas

Requests for reprints: Anil K. Sood, Departments of Gynecologic Oncology and Cancer Biology, The University of Texas M. D. Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030. Phone: 713-745-5266; Fax: 713-792-7586; E-mail: asood{at}mdanderson.org.

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.

This article has been cited by other articles:

				Y. G. Lin, A. Immaneni, W. M. Merritt, L. S. Mangala, S. W. Kim, M. M.K. Shahzad, Y. T.M. Tsang, G. N. Armaiz-Pena, C. Lu, A. A. Kamat, et al. Targeting Aurora Kinase with MK-0457 Inhibits Ovarian Cancer Growth Clin. Cancer Res., September 1, 2008; 14(17): 5437 - 5446. [Abstract] [Full Text] [PDF]

				A. Klein, D. Flugel, and T. Kietzmann Transcriptional Regulation of Serine/Threonine Kinase-15 (STK15) Expression by Hypoxia and HIF-1 Mol. Biol. Cell, September 1, 2008; 19(9): 3667 - 3675. [Abstract] [Full Text] [PDF]

				O. Gautschi, J. Heighway, P. C. Mack, P. R. Purnell, P. N. Lara Jr., and D. R. Gandara Aurora Kinases as Anticancer Drug Targets Clin. Cancer Res., March 15, 2008; 14(6): 1639 - 1648. [Abstract] [Full Text] [PDF]