title: Promoter methylation status and expression of estrogen receptor alpha in familial breast cancer patients.
abstract: The hypermethylation of estrogen receptor alpha (ERα) promoter is a common molecular alteration in sporadic breast cancer (BC), but its involvement in familial BC remains largely unknown. In the present study, we analyzed the methylation statuses of four regions (ER1, ER3, ER4, and ER5) of the ERα promoter and the ERα expression levels of 113 familial BC patients in a Han Chinese Population from northeastern China and evaluated the association between major clinicopathological features and the hypermethylation statuses of the ERα gene. Tumor samples were analyzed for ERα methylation status by the methylation-specific polymerase chain reaction for ERα, PR, p53, BRCA-1, and BRCA-2 by immunohistochemical (IHC) staining and for Her-2 status by IHC and fluorescence in situ hybridization (FISH). ERα methylation was observed in tumor tissues in 47/113 (41.6%) familial BC patients. There were no significant differences in the methylation statuses among ER1 (20.4%), ER3 (18.6%), ER4 (17.7%), and ER5 (19.5%; χ (2) = 3.89, p > 0.05). An association between ERα expression level and its promoter methylation level was found. In addition, ERα methylation was significantly correlated with tumor size, PR expression, p53 nuclear accumulation, and BRCA-1 and BRCA-2 statuses. In conclusion, in familial BC patients, the level of ERα gene promoter methylation correlates with ERα expression, PR, p53 nuclear accumulation, and BRCA-1 and BRCA-2 statuses. Epigenetic alteration of ERα gene may play an important role in the pathogenesis of familial BC.
authors.affiliation: Departments of Breast Surgery and Surgical Oncology, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, 110001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Mao
authors.forename: Min-jie
authors.initials: MJ
authors.lastname: Wei
authors.forename: Fan
authors.initials: F
authors.lastname: Yao
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D002681:China; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005192:Family Health; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha