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

      Clinical cancer research : an official journal of the American Association for Cancer Research

      Adult, Aged, Aged, 80 and over, Antineoplastic Agents, therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Aurora Kinases, Cell Line, Tumor, Centrosome, enzymology, pathology, Female, Humans, Immunohistochemistry, Middle Aged, Neoplasm Staging, Ovarian Neoplasms, drug therapy, mortality, Prognosis, Protein-Serine-Threonine Kinases, genetics, Survival Analysis

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          Abstract

          To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma. 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. 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. 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.

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          Journal
          17634535
          10.1158/1078-0432.CCR-07-0431

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