Methylation of tumor suppressor gene p16 and prognosis of epithelial ovarian cancer

Objective. Methylation of p16 promoter was evaluated in ovarian cancer to determine the role of p16 methylation in ovarian cancer prognosis. Methods. Two hundred and forty-nine patients with primary epithelial ovarian cancer were selected for the study; these patients were followed for a median of 31 months. Genomic DNA extracted from fresh frozen tumor tissues were treated with sodium bisulfite and were analyzed for p16 methylation using methylation-specific PCR (MSP). Cox regression survival analysis was performed to examine the associations of p16 methylation with progression-free and overall survivals. Results. Of the 249 patients, 100 (40%) were tested positive for p16 promoter methylation. The status of p16 methylation did not change significantly with patient age, disease stage, histological grade, residual tumor size, and debulking results, although p16 methylation seemed to occur more often in patients with advanced diseases or aggressive tumors. Compared to those without p16 methylation, patients with p16 methylation had significantly higher risk for disease progression (P = 0.01). The relative risk for progression was 1.69 (95% Cl: 1.12-2.54), and the association remained statistically significant (RR = 1.54, 95% Cl: 1.01 -2.34) after adjusting for clinical and pathological variables. The risk for death was also higher in methylation positive patients than in methylation negative patients (RR = 1.33, 95% Cl: 0.88-2.00), but the difference was not statistically significant. Conclusion. The study suggests that promoter methylation in the p16 gene is associated with ovarian cancer progression, and evaluation of p16 methylation may have values in predicting ovarian cancer prognosis. (C) 2004 Elsevier Inc. All rights reserved.