Prognostic impact of p53, p27, and C-MYC on clinicopathological features and outcome in early-stage (FIGO I-II) epithelial ovarian cancer.

Introduction: The objective of the study was to evaluate the prognostic effect of p53, p27, and C-MYC on clinicopathological features, recurrent disease, and disease-free survival (DFS) of 131 patients with ovarian cancer in International Federation of Gynecology and Obstetrics (FIGO) stages I-II.

Methods: The technique of tissue microarray and immunohistochemistry was used for detection of positivity/overexpression of the biological markers p53, p27, and C-MYC.

Results: In the complete series, the 5-year and overall survival rates were 68% and 71%, respectively. Positive staining for p53, p27, and C-MYC was detected in 25%, 57%, and 76% of cases, respectively. Positivity of p53, p27, concomitant p53-p27, C-MYC, and C-MYC-p27 status were associated with tumor grade. Positivity of p27 and concomitant p53-p27 were related to serous tumors. In survival analysis, DFS was related to p53, combined p53-p27, and combined p53-C-MYC status. Significant predictive factors for tumor recurrences were the FIGO stage (odds ratio [OR] = 9.8), status of node sampling (OR = 0.2), and p53 status (OR = 3.7) in a logistic regression analysis. In a multivariate Cox regression analysis, FIGO stage (hazard ratio [HR] = 4.3) and p53 status (HR = 3.0) were significant prognostic factors for DFS. In a separate Cox regression analysis, FIGO stage (HR = 2.0) and concomitant p53-p27-C-MYC status (HR = 0.3) were independent prognostic factors for DFS. It was possible to identify a subgroup, constituting 30% of the patients, who had excellent survival with tumors of concomitant p53 negativity, p27 positivity, and C-MYC positivity apart from the clinicopathological factors. Patients in this subgroup were longtime survivors with DFS of 92% at 5 and 9 years.

Conclusions: The results of this study strongly suggest that patients with p53-positive tumors (alone/or combined with p27 and/or C-MYC) had significantly worse survival (DFS) compared with patients with p53-negative tumors. Patients with p53-positive tumors continued to have recurrences after the 5-year follow-up and die in disease.