TY - JOUR
T1 - Overexpression of the centrosomal protein Aurora-A kinase is associated with poor prognosis in epithelial ovarian cancer patients
AU - Landen, Charles N.
AU - Lin, Yvonne G.
AU - Immaneni, Anand
AU - Deavers, Michael T.
AU - Merritt, William M.
AU - Spannuth, Whitney A.
AU - Bodurka, Diane C.
AU - Gershenson, David M.
AU - Brinkley, William R.
AU - Sood, Anil K.
PY - 2007/7/15
Y1 - 2007/7/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34547109084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547109084&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-07-0431
DO - 10.1158/1078-0432.CCR-07-0431
M3 - Article
C2 - 17634535
AN - SCOPUS:34547109084
SN - 1078-0432
VL - 13
SP - 4098
EP - 4104
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -