ESR-alpha promoter methylation to predict survival in low-grade ovarian cancer.

Abstract

e15529 Background: Ovarian cancer is one of the most lethal gynecologic malignancies and the leading cause of death among women with gynecological cancers. Different molecular markers have been studied for their prognostic relevance, but to date only CA 12-5 is used in routine diagnostic. Aberrant methylation of the estrogen receptor promoter (ESRp) was first described in colorectal cancer. Previous studies that described methylation of the ESRp in ovarian cancer suggested a potential role in cancer development. The aim of this study was to examine the methylation of the ESRp in a cohort of ovarian cancer patients in regard to its prognostic relevance. Methods: The study cohort consisted of 77 ovarian cancer patients that were diagnosed between 2000 and 2009 at the Department of OBGYN of the LMU Munich. A total of 50 patients died, 25 are still alive, 2 were lost to follow-up. Genomic DNA was isolated from paraffin-embedded cancer tissue and followed by bisulfite treatment. For detection of the methylated ESRp we used a sensitive real-time PCR. Results: Survival was significantly shorter for patients with aberrant promoter methylation within the subgroup of borderline, G1 and G2 tumors (31 patients; survival for methylated cases was 3.48 vs 4.91 years for unmethylated cases (p=0.010)). Within the small subgroup of borderline and G1 tumors (10 patients) survival for methylated cases was 4.73 vs 6.08 years for unmethylated cases (p=0.014). No significant difference of survival was observed for high grade (G3) ovarian cancer patients (p=0.745). Conclusions: We demonstrated for the first time that the methylation status of the ESRp might be a promising prognostic marker in ovarian cancer. ESRp methylation does not seem to be of prognostic relevance in high-grade ovarian cancer. In our study cohort a three-step grading system was used, but recent publications favor a two-step grading system. Thus, the G2 cases should be reevaluated to see whether they are G1 or G3. The difference in tumor etiology of low and high grade ovarian cancer might be responsible for the different prognostic relevance of ESRp methylation. Since our subgroup of borderline and G1 tumors is very small, these are preliminary results that have to be confirmed in a larger patient cohort.