DeltaNp63 expression is associated with poor survival in ovarian cancer.
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 deltaNp63 in ovarian cancer biopsies to correlate their expression with clinical outcome.


METHODS
Real-time RT-PCR analysis was used to determine the levels of TAp63 and deltaNp63 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 deltaNp63 levels increased 77-fold in stage III, independently of the p53 status. Patients with high deltaNp63 expression had the worst overall survival (OS); patients with a deltaNp63/TAp63 ratio >2 had a poor OS. Patients with a high deltaNp63/TAp63 ratio were those with a poor response to platinum-based therapy.


CONCLUSIONS
Data indicate a role for deltaNp63 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.
Marchini
S
S
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. marchini@marionegri.it
Marabese
M
M
Marrazzo
E
E
Mariani
P
P
Cattaneo
D
D
Fossati
R
R
Compagnoni
A
A
Fruscio
R
R
Lissoni
A A
AA
Broggini
M
M
D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D015534:Trans-Activators / Q000032:analysis*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000032:analysis*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins