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Annals of Oncology Advance Access published online on November 12, 2007
Annals of Oncology, doi:10.1093/annonc/mdm519
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© 2007 European Society for Medical Oncology

{Delta}Np63 expression is associated with poor survival in ovarian cancer

S. Marchini1,3,*,{dagger}, M. Marabese1,{dagger}, E. Marrazzo1, P. Mariani1, D. Cattaneo1, R. Fossati2, A. Compagnoni2, R. Fruscio3, A. A. Lissoni3 and M. Broggini1

1 Laboratory of Molecular Pharmacology
2 Department of Oncology, Laboratory of Translational Research and Clinical Outcome, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan
3 Ospedale San Gerardo, Universita’ di Milano Bicocca, Monza, Italy

* Correspondence to: Dr S. Marchini, Department of Oncology, Laboratory of Molecular Pharmacology, via La Masa 19, 20156 Milan, Italy. Tel: +3902-39014236; Fax +3902-3546277; E-mail: marchini{at}marionegri.it

Background: P63 belongs to the ‘p53 family’ whose role in cancer progression has been recently revisited in light of the plethora of splicing variants that are generated. We analyzed the expression of the full-length TAp63 gene and its dominant-negative form {Delta}Np63 in ovarian cancer biopsies to correlate their expression with clinical outcome.

Materials and methods: Real-time RT–PCR analysis was used to determine the levels of TAp63 and {Delta}Np63 in 83 stage I and in 86 stage III ovarian cancer biopsies and in seven human ovarian cancer cell.

Results: TAp63 levels were comparable in stage I and stage III, but {Delta}Np63 levels increased 77-fold in stage III, independently of the p53 status. Patients with high {Delta}Np63 expression had the worst overall survival (OS); patients with a {Delta}Np63/TAp63 ratio >2 had a poor OS. Patients with a high {Delta}Np63/TAp63 ratio were those with a poor response to platinum-based therapy.

Conclusions: Data indicate a role for {Delta}Np63 as a potential biomarker to predict patient's outcome and tumor progression in ovarian cancer. This would have particularly clinical relevance in ovarian cancer where the high rate of mortality reflects our lack of knowledge of molecular mechanisms underlying cell progression toward malignancy.

epithelial ovarian cancer, p53 family, p63

{dagger} Both the authors contributed equally to this work.

Received for publication July 10, 2007. Revision received October 9, 2007. Accepted for publication October 9, 2007.


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