title: Estrogen receptor-alpha methylation predicts melanoma progression.
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.
authors.affiliation: Department of Molecular Oncology, Division of Surgical Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
authors.forename: Takuji
authors.initials: T
authors.lastname: Mori
authors.forename: Steve R
authors.initials: SR
authors.lastname: Martinez
authors.forename: Steven J
authors.initials: SJ
authors.lastname: O'Day
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Umetani
authors.forename: Minoru
authors.initials: M
authors.lastname: Kitago
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanemura
authors.forename: Sandy L
authors.initials: SL
authors.lastname: Nguyen
authors.forename: Andy N
authors.initials: AN
authors.lastname: Tran
authors.forename: He-Jing
authors.initials: HJ
authors.lastname: Wang
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
mesh_terms: D000367:Age Factors; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D000077209:Decitabine; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012737:Sex Factors
chemical_list: D004273:DNA, Neoplasm; D047628:Estrogen Receptor alpha; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine