Association between the N-terminally truncated (DeltaN) p63alpha (DeltaNp63alpha) isoform and debulking status, VEGF expression and progression-free survival in previously untreated, advanced stage epithelial ovarian cancer: A Gynecologic Oncology Group study.
OBJECTIVE
The Gynecologic Oncology Group (GOG) examined the association between the relative expression of the DeltaNp63alpha isoform and clinicopathologic variables, p53 status, angiogenic markers, progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC).


METHODS
Immunoblot analysis was used to determine the relative expression of DeltaNp63alpha to beta-actin in lysates of frozen primary tumor from women with previously untreated, advanced stage EOC who participated in a GOG specimen banking protocol and a randomized phase III treatment protocol.


RESULTS
DeltaNp63alpha was detected in 49/56 (87.5%) cases with relative expression ranging from 0 to 4.55 (median=0.325). A correlation was observed between the relative expression of DeltaNp63alpha and debulking status (Spearman's correlation coefficient=0.303; p=0.025) and the relative expression of vascular endothelial growth factor (VEGF) (Spearman's correlation coefficient=0.303; p=0.045), but not with p53 status (overexpression or mutation), immunoblot expression of MASPIN, or the relative expression of thrombospondin-1, basic fibroblast growth factor or VEGF receptor-1. A 1.4-fold increase was observed in the risk of disease progression for each unit increase in the relative expression of DeltaNp63alpha using an unadjusted (hazard ratio [HR]=1.459; 95% confidence interval [CI]=1.096-1.942; p=0.010), a full (HR=1.483; 95% CI=1.060-2.076; p=0.021) and a reduced (HR=1.387; 95% CI=1.025-1.877; p=0.034) Cox regression model. The relative expression of DeltaNp63alpha was not associated with OS using an unadjusted, a full or a reduced Cox model.


CONCLUSIONS
The relative expression DeltaNp63alpha appears to be associated with debulking status and the relative expression of VEGF and PFS, and to be an independent prognostic factor for disease progression in EOC.
Jewell
Elizabeth L
EL
Duke University Medical Center 3079, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. jewelle@mskcc.org
Darcy
Kathleen M
KM
Hutson
Alan
A
Lee
Paula S
PS
Havrilesky
Laura J
LJ
Grace
Lisa A
LA
Berchuck
Andrew
A
Secord
Angeles Alvarez
AA
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms; D016032:Randomized Controlled Trials as Topic; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020033:Protein Isoforms; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A