Association of Poor Prognosis Subtypes of Breast Cancer with Estrogen Receptor Alpha Methylation in Iranian Women


Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarraycan classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normallikewhich have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markersincluding estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 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-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have beencharacterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathwayin mammary cell proliferation; it appears that epigenetic changes in the ERα gene as a central component of thispathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of differentIHC-based subtypes of breast tumors with ERα methylation in Iranian breast cancer patients. For this purposeone hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessedment oftheir ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypesaccording to IHC markers and data were collected on pathological features of the patients. ERα methylation wasfound in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and7 of 14 (50%) luminal B tumors. A strong correlation was found between ERα methylation and poor prognosistumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that ERα methylation is correlatedwith poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesisof the more aggressive breast tumors.