Estrogen receptor promoter methylation predicts survival in low-grade ovarian carcinoma patients

J Cancer Res Clin Oncol. 2014 Oct;140(10):1681-7. doi: 10.1007/s00432-014-1729-9. Epub 2014 Jun 8.

Abstract

Purpose: Ovarian carcinoma is the third most common gynecological cancer and only short recurrence-free survival and overall survival times are achieved. The role of the estrogen receptor expression is well studied in breast cancer and breast cancer cell lines. Patients with positive estrogen receptor expression have a lower risk for recurrence and a better overall survival. Previous studies have shown that ESR1 methylation influences ovarian cancer development and might thus play a role regarding prognosis of ovarian carcinoma.

Methods: A total of 75 patients were identified that were treated for ovarian carcinoma by debulking surgery and adjuvant standard chemotherapy. Isolation and bisulfite treatment of genomic DNA from serial sections of surgically resected ovarian carcinoma tissue was performed using commercially available kits. For the detection of methylated ESR1 promoter sequences, real-time methylation-specific PCR was used.

Results: Promoter methylation did not show a correlation between clinical-pathological data for all patients. However, within the subgroup of low-grade ovarian carcinoma patients and patients with an ovarian tumor of low malignant potential methylation of the ESR1 promoter inversely correlated with survival (p = 0.031).

Conclusions: Although small numbers of ovarian carcinoma patients were analyzed, methylation status might be useful as a prognostic marker within the subgroup of low-grade ovarian carcinoma patients. Further studies should investigate a larger cohort and also address the use of demethylation agents with respect to improve patient's prognosis in this subgroup of ovarian carcinoma patients.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • DNA Methylation*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Grading
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology*
  • Predictive Value of Tests
  • Promoter Regions, Genetic / genetics
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • ESR1 protein, human
  • Estrogen Receptor alpha