Estrogen receptor-alpha methylation predicts melanoma progression

Cancer Res. 2006 Jul 1;66(13):6692-8. doi: 10.1158/0008-5472.CAN-06-0801.

Abstract

The role of estrogen receptor alpha (ER-alpha) in melanoma is unknown. ER-alpha expression may be regulated in melanoma via hypermethylation of promoter CpG islands. We assessed ER-alpha hypermethylation in primary and metastatic melanomas and sera as a potential tumor progression marker. ER-alpha methylation status in tumor (n = 107) and sera (n = 109) from American Joint Committee on Cancer (AJCC) stage I to IV melanoma patients was examined by methylation-specific PCR. The clinical significance of serum methylated ER-alpha was assessed among AJCC stage IV melanoma patients receiving biochemotherapy with tamoxifen. Rates of ER-alpha methylation in AJCC stage I, II, and III primary melanomas were 36% (4 of 11), 26% (5 of 19), and 35% (8 of 23), respectively. Methylated ER-alpha was detected in 42% (8 of 19) of stage III and 86% (30 of 35) of stage IV metastatic melanomas. ER-alpha was methylated more frequently in metastatic than primary melanomas (P = 0.0003). Of 109 melanoma patients' sera in AJCC stage I, II, III, and IV, methylated ER-alpha was detected in 10% (2 of 20), 15% (3 of 20), 26% (5 of 19), and 32% (16 of 50), respectively. Serum methylated ER-alpha was detected more frequently in advanced than localized melanomas (P = 0.03) and was the only factor predicting progression-free [risk ratio (RR), 2.64; 95% confidence interval (95% CI), 1.36-5.13; P = 0.004] and overall survival (RR, 2.31; 95% CI, 1.41-5.58; P = 0.003) in biochemotherapy patients. Hypermethylated ER-alpha is a significant factor in melanoma progression. Serum methylated ER-alpha is an unfavorable prognostic factor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • DNA Methylation*
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics
  • Decitabine
  • Disease Progression
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Silencing
  • Humans
  • Hydroxamic Acids / pharmacology
  • Male
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Middle Aged
  • Neoplasm Staging
  • Promoter Regions, Genetic
  • Sex Factors

Substances

  • DNA, Neoplasm
  • Estrogen Receptor alpha
  • Hydroxamic Acids
  • trichostatin A
  • Decitabine
  • Azacitidine