Association between the N-terminally truncated (ΔN) p63α (ΔNp63α) isoform and debulking status, VEGF expression and progression-free survival in previously untreated, advanced stage epithelial ovarian cancer: A Gynecologic Oncology Group study

Abstract

Objectives The Gynecologic Oncology Group (GOG) examined the association between the relative expression of the ΔNp63α 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 ΔNp63α to β-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 ΔNp63α 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 ΔNp63α 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 ΔNp63α 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 ΔNp63α was not associated with OS using an unadjusted, a full or a reduced Cox model. Conclusions The relative expression ΔNp63α 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.