title: Estrogen receptor alpha phosphorylated at tyrosine 537 is associated with poor clinical outcome in breast cancer patients treated with tamoxifen.
abstract: 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.
authors.affiliation: Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, R3E 0V9, MB, Canada.
authors.forename: Georgios P
authors.initials: GP
authors.lastname: Skliris
authors.forename: Zoann
authors.initials: Z
authors.lastname: Nugent
authors.forename: Peter H
authors.initials: PH
authors.lastname: Watson
authors.forename: Leigh C
authors.initials: LC
authors.lastname: Murphy
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014443:Tyrosine