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

Charles N. Landen, Yvonne G. Lin, Anand Immaneni, Michael T. Deavers, William M. Merritt, Whitney A. Spannuth, Diane C. Bodurka, David M. Gershenson, William R. Brinkley, Anil K. Sood

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4098-4104
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number14
DOIs
StatePublished - Jul 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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