title: CpG island methylation profile of estrogen receptor alpha in Iranian females with triple negative or non-triple negative breast cancer: new marker of poor prognosis.
abstract: One decade early onset of the breast cancer in Iranian females was reported but the basis of the observed difference has remained unclear and difference in gene silencing by epigenetic processes is suggested. Hence, this study was sought to map the methylation status of ER gene CpG islands and its impact on clinicopathological factors of triple negative and non-triple negative ductal cell carcinoma of the breast in Iranian females. Surgically resected formalin-fixed paraffin-embedded breast tissues from sixty Iranian women with confirmed invasive ductal carcinoma were assessed by methylation-specific PCR using primer sets encompassing some of the 29 CpGs across the ER gene CpG island. The estrogen and progesterone receptors, Her-2 overexpression, and nuclear accumulation of P53 were examined using immunohistochemistry (IHC). Methylated ER3, ER4, and ER5 were found in 41.7, 11.3, and 43.3% of the samples, respectively. Significantly higher methylation of ER4 was found in the tumors with nuclear accumulation of P53, and significantly higher methylation of ER5 was found in patients with lymph node involvement and tumor with bigger size or higher grades. Furthermore, significantly higher rate of ER5 methylation was found in patients with Her-2+ tumors and in postmenopausal patients with ER-, PgR-, or ER-/PgR- tumors. However, no significant difference in ERs methylation status was found between triple negative and non-triple negative tumors in pre- and postmenopausal patients. Findings revealed that aberrant hypermethylation of ER-a gene frequently occur in Iranian women with invasive ductal cell carcinoma of the breast. However, methylation of different CpG islands produced a diverse impact on the prognosis of breast cancer, and ER5 was found to be the most frequently methylated region in the Iranian women, and could serve as a marker of poor prognosis.
authors.affiliation: Department of Clinical Biochemistry and Nutrition, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ramezani
authors.forename: Siamak
authors.initials: S
authors.lastname: Salami
authors.forename: Mir Davood
authors.initials: MD
authors.lastname: Omrani
authors.forename: Davood
authors.initials: D
authors.lastname: Maleki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D007492:Iran; D008593:Menopause; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human