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

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 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: Charles N Landen Jr, 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 14 Pg. 4098-104 (Jul 15 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17634535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Aurora Kinases
• Protein Serine-Threonine Kinases

Topics

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