Prognostic Impact of Concomitant p53 and PTEN on Outcome in Early Stage (FIGO I-II) Epithelial Ovarian Cancer

Abstract

The objective of the study was to evaluate the prognostic effect of p53, PTEN, and concomitant p53 PTEN status on clinicopathologic features, recurrent disease, and disease-free survival (DFS) of 131 patients in FIGO stages I to II with epithelial ovarian cancer. The technique of tissue microarray and immunohistochemistry was used for the detection of positivity of the biologic markers p53 and PTEN. In the complete series, the 5-year DFS rate was 68%, and the overall survival rate was 71%. Positive staining for p53 and PTEN was detected in 25% and 22% of cases, respectively. Positivity of p53 was associated with tumor grade in the total series but not in the subgroup of serous tumors. In survival analysis, there was worse survival (P = 0.003) in the group of patients with p53-positive tumors compared with the group of patients with p53-negative tumors with DFS of 62% and 82%, respectively. Furthermore, DFS was 15% for the subgroup of patients with concomitant p53-positivity and PTEN-negativity of tumors compared with DFS of 62% for others in 1 group (p53+PTEN+, p53-PTEN+, p53-PTEN-) at 100 months. The difference was highly significant (P = 0.006). FIGO stage (odds ratio = 8.0) and p53 PTEN status (odds ratio = 0.6) were predictive factors for tumor recurrences in a logistic regression and prognostic factors with hazard ratios (HRs) of 4.0 and 0.6, respectively, in a multivariate Cox regression analysis. In a separate Cox regression analysis, FIGO stage (HR = 3.6) and p53 status (HR = 2.0) were prognostic factors for DFS. For serous tumors (n = 51) recurrent disease was associated with FIGO stage (P = 0.013), and p53 loss (P = 0.029) but not with FIGO grade (P = 0.169). p53 status divides ovarian carcinomas into 2 subgroups after prognosis, also in serous tumors. Presence of PTEN in p53-positive tumors seems to protect from bad prognosis and absence of PTEN seems to worsen prognosis in early stages.