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.
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.
Authors: Gong Yang; Bin Chang; Fan Yang; Xiaoqing Guo; Kathy Qi Cai; Xue Sherry Xiao; Huamin Wang; Subrata Sen; Mien-Chie Hung; Gordon B Mills; Sandy Chang; Asha S Multani; Imelda Mercado-Uribe; Jinsong Liu Journal: Clin Cancer Res Date: 2010-04-27 Impact factor: 12.531
Authors: Dongjiu Ye; Guillermo Garcia-Manero; Hagop M Kantarjian; Lianchun Xiao; Saroj Vadhan-Raj; Michael H Fernandez; Martin H Nguyen; L Jeffrey Medeiros; Carlos E Bueso-Ramos Journal: J Hematop Date: 2008-11-04 Impact factor: 0.196
Authors: Zheng Fu; Kevin Regan; Lizhi Zhang; Michael H Muders; Stephen N Thibodeau; Amy French; Yanhong Wu; Scott H Kaufmann; Wilma L Lingle; Junjie Chen; Donald J Tindall Journal: J Clin Invest Date: 2009-08-17 Impact factor: 14.808
Authors: T-V Do; F Xiao; L E Bickel; A J Klein-Szanto; H B Pathak; X Hua; C Howe; S W O'Brien; M Maglaty; J A Ecsedy; S Litwin; E A Golemis; R J Schilder; A K Godwin; D C Connolly Journal: Oncogene Date: 2013-01-21 Impact factor: 9.867