title: Expression of androgen receptor and its phosphorylated forms in breast cancer progression.
abstract: BACKGROUND
  Androgen receptor (AR) expression in breast cancers may serve as a prognostic and predictive marker. We examined the expression pattern of AR and its phosphorylated forms, Ser-213 (AR-Ser[P]-213) and Ser-650 (AR-Ser[P]-650), in breast cancer and evaluated their association with clinicopathological parameters.
  
  
  METHODS
  Immunohistochemistry was performed on primary and distant metastatic breast cancers and benign breast tissue using antibodies against AR, AR-Ser(P)-213, and AR-Ser(P)-650. The levels of cytoplasmic and nuclear expression were scored semiquantitatively using a histoscore.
  
  
  RESULTS
  Nuclear staining of AR was observed in all benign breast tissue and 67% of cancer cases. Nuclear and cytoplasmic AR-Ser(P)-213 was increased in breast cancers 2-fold (P = .0014) and 1.7-fold (P = .05), respectively, compared with benign controls, whereas nuclear and cytoplasmic AR-Ser(P)-650 expression was decreased in tumors by 1.9-fold and 1.7-fold (both P < .0001), respectively. Increased expression of nuclear or cytoplasmic AR-Ser(P)-213 was observed in metastatic breast cancers (1.3-fold, P = .05), ER-negative (2.6-fold, P = .001), and invasive ductal carcinoma (6.8-fold, P = .04). AR-Ser(P)-650 expression was downregulated in lymph node-positive breast cancers (1.4-fold, P = .02) but was upregulated in invasive ductal carcinomas (3.2-fold, P < .0001) and metastases (1.5-fold, P = .003). Moreover, in ER-negative breast cancers, nuclear AR-Ser(P)-650 was decreased (1.4-fold, P = .005), and cytoplasmic AR-Ser(P)-650 was increased (1.4-fold, P = .003).
  
  
  CONCLUSIONS
  AR and its phosphorylation at serines 213 and 650 are differentially expressed in breast cancer tumorigenesis and progression. Phosphorylation of AR at serines 213 and 650 is increased in ER-negative breast cancers, ductal carcinomas, and metastases and may have predictive value in breast cancer prognosis.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY.
authors.forename: Qinghu
authors.initials: Q
authors.lastname: Ren
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Urology, New York University School of Medicine, New York, NY.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY.
authors.forename: Rachel
authors.initials: R
authors.lastname: Ruoff
authors.affiliation: Department of Urology, New York University School of Medicine, New York, NY.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY.
authors.forename: Susan
authors.initials: S
authors.lastname: Ha
authors.affiliation: Department of Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY.|Department of New York University Cancer Institute, New York, NY.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Victor
authors.initials: V
authors.lastname: Reuter
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: William
authors.initials: W
authors.lastname: Gerald
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Dilip D
authors.initials: DD
authors.lastname: Giri
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.affiliation: Department of Urology, New York University School of Medicine, New York, NY.|Department of Microbiology, New York University School of Medicine, New York, NY.|Department of New York University Cancer Institute, New York, NY.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Garabedian
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY.|Department of Urology, New York University School of Medicine, New York, NY.|Department of New York Harbor Healthcare System, New York, NY.|Department of New York University Cancer Institute, New York, NY.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Urology, New York University School of Medicine, New York, NY.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY.|Department of New York University Cancer Institute, New York, NY.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Logan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C410798:AR protein, human; C508053:ERBB2 protein, human
keywords: androgen; androgen receptor; breast; breast neoplasms; phosphorylation