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A phospho-tyrosine 537-ERα (p-Y537-ERα) antibody was validated for immunohistochemistry of formalin-fixed paraffin-embedded human breast cancer biopsies and used to interrogate multiple ER positive breast cancer cases present on tissue microarrays already constructed by the Manitoba Breast Tumor Bank. Nuclear p-Y537-ERα protein expression was positively associated with positive nodes (Spearman r = 0.20, P = 0.0002) and large tumor size (r = 0.13, P = 0.02). On univariate analysis, high levels of p-Y537 were associated with poor overall survival (HR = 1.65, 95% CI 1.08-2.52, P = 0.02) but not relapse free survival from breast cancer. The association with overall survival was not significant on multivariate analysis. These data support the relevance of phosphorylation at p-Y537-ERα in human breast cancers and add further support to the presence of a phosphorylation code for ERα in human breast cancer in vivo.

Estrogen Receptor Alpha Phosphorylated at Tyrosine 537 is Associated with Poor Clinical Outcome in Breast Cancer Patients Treated with Tamoxifen