Estrogen receptor-α methylation predicts melanoma progression

Takuji Mori, Steve R. Martinez, Steven J. O'Day, Donald L. Morton, Naoyuki Umetani, Minoru Kitago, Atsushi Tanemura, Sandy L. Nguyen, Andy N. Tran, He Jing Wang, Dave S.B. Hoon

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Abstract

The role of estrogen receptor α (ER-α) in melanoma is unknown. ER-α expression may be regulated in melanoma via hypermethylation of promoter CpG islands. We assessed ER-α hypermethylation in primary and metastatic melanomas and sera as a potential tumor progression marker. ER-α 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-α was assessed among AJCC stage IV melanoma patients receiving biochemotherapy with tamoxifen. Rates of ER-α 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-α was detected in 42% (8 of 19) of stage III and 86% (30 of 35) of stage IV metastatic melanomas. ER-α 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-α was detected in 10% (2 of 20), 15% (3 of 20), 26% (5 of 19), and 32% (16 of 50), respectively. Serum methylated ER-α 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-α is a significant factor in melanoma progression. Serum methylated ER-α is an unfavorable prognostic factor.

Original languageEnglish
Pages (from-to)6692-6698
Number of pages7
JournalCancer Research
Volume66
Issue number13
DOIs
Publication statusPublished - 2006 Jul 1
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mori, T., Martinez, S. R., O'Day, S. J., Morton, D. L., Umetani, N., Kitago, M., Tanemura, A., Nguyen, S. L., Tran, A. N., Wang, H. J., & Hoon, D. S. B. (2006). Estrogen receptor-α methylation predicts melanoma progression. Cancer Research, 66(13), 6692-6698. https://doi.org/10.1158/0008-5472.CAN-06-0801