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

Estrogen receptor-alpha methylation predicts melanoma progression

Takuji Mori  1 , 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
Affiliations

Estrogen receptor-alpha methylation predicts melanoma progression

Takuji Mori et al. Cancer Res. .

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.

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Figures

Figure 1
Figure 1
Representative expression and reexpression of ER-α in three melanoma lines (MCA, MCB, and MCC) treated with 5-aza-CdR and TSA. mRNA expression was analyzed by RT-PCR. The housekeeping gene GAPDH was included as a RT-PCR control. NT, cell line not treated with 5-aza-CdR and TSA; T, cell line treated with 5-aza-CdR and TSA.
Figure 2
Figure 2
Representative methylation-specific PCR results of melanoma cell line (MCA) with and without 5-aza-CdR plus TSA treatment. M, methylated-specific product; U, unmethylated-specific product. Only a methylated peak was initially observed (untreated). An unmethylated peak appeared after treatment with 5-aza-CdR plus TSA (treated).
Figure 3
Figure 3
A, frequency of methylated ER-α DNA in melanoma tumors according to AJCC stage. Prim, primary melanoma tumor; Met, metastatic melanoma tumor. B, frequency of methylated ER-α DNA in melanoma patients’ sera according to AJCC stage. Norm <50, normal healthy volunteers younger than 50 years. Norm ≥60, normal healthy volunteers ages 60 years or older.
Figure 4
Figure 4
Representative methylation-specific PCR results of sera and tissue specimens. No methylation peak appeared in serum of healthy donor (A). A methylation peak appeared in normal liver tissue (B). A single methylation peak was detected in sera and paraffin-embedded specimens from stage IV melanoma patients (C–H). E and F, paired specimens from the same patient.
Figure 5
Figure 5
A, Kaplan-Meier curves showing the correlation of pre-biochemotherapy serum ER-α methylation status with progression-free survival (Cox proportional hazard, P = 0.004). Methylated, patients with serum methylated ER-α DNA. No methylation, patients with no detectable serum methylated ER-α. B, Kaplan-Meier curves showing the correlation of pre-biochemotherapy serum ER-α methylation status with overall survival (Cox proportional hazard, P = 0.003).
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References

    1. Balch CM, Soong SJ, Atkins MB, et al. An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin. 2004;54:131–149. - PubMed
    1. Dulaimi E, Hillinck J, Ibanez de Caceres I, Al-Saleem T, Cairns P. Tumor suppressor gene promoter hyper-methylation in serum of breast cancer patients. Clin Cancer Res. 2004;10:6189–6193. - PubMed
    1. Jeronimo C, Henrique R, Hoque MO, et al. A quantitative promoter methylation profile of prostate cancer. Clin Cancer Res. 2004;10:8472–8478. - PubMed
    1. Lapidus RG, Ferguson AT, Ottaviano YL, et al. Methylation of estrogen and progesterone receptor gene 5′ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res. 1996;2:805–810. - PubMed
    1. Shinozaki M, Hoon DS, Giuliano AE, et al. Distinct hypermethylation profile of primary breast cancer is associated with sentinel lymph node metastasis. Clin Cancer Res. 2005;11:2156–2162. - PubMed

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