Association of poor prognosis subtypes of breast cancer with estrogen alpha methylation in Iranian women

Gene expression profiling by DNA microarray can classify breast tumors in tofive different molecular subtypes: luminal A, luminal B, HER-2, basal andnormal-like. These various subtypes have different prognosis. Recently it hasbeen shown that immunohistochemistry (IHC) markers include estrogenreceptor (ER), progesterone receptor (PR) and human epidermal growth factorreceptor 2 (Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-;HER-2-), luminal B (ER+;PR+/-; HER-2+), basal-like (ER-;PR-;HER2-) andHer2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype havebeen characterized by poor prognosis and reduced overall survival. Due to theimportance of ER signaling pathway in mammary cells proliferation; it seemsthat epigenetic changes in ERα gene as a central part of this pathway, maycontribute to prognostication of breast tumors. Thus this study aimed to clarifythe correlation of different IHC-based subtypes of breast tumors with ERαmethylation in Iranian breast cancer patients. For this purpose one hundred freshbreast tumors obtained by surgical resection and after DNA extraction their ERmethylation status were assessed by methylation specific PCR (MSP). A strongcorrelation was found between ERα methylation and poor prognosis tumorsubtypes (basal and Her2+) in patients (P< 0.001). Our findings showed thatERα methylation is correlated with poor prognosis subtypes of breast tumors inIranian patients and may play an important role in pathogenesis of the moreaggressive breast tumors.