title: Androgen receptor expression is usually maintained in initial surgically resected breast cancer metastases but is often lost in end-stage metastases found at autopsy.
abstract: Androgen receptor (AR) is expressed in approximately 70% of primary breast carcinomas (PBCs) and is a promising therapeutic target for metastatic breast carcinoma (MBC). Here, we examine AR expression in a population of initial surgically resected metastases and a separate cohort of end-stage metastases harvested at autopsy compared with their matched PBCs. Tissue microarrays of matched PBC and MBC were labeled by immunohistochemistry for AR, estrogen receptor (ER), progesterone receptor (PR), and Her2 and classified into the following previously described categories: luminal (ER/PR+/Her2-), triple negative (ER/PR/Her2-), Her2 (ER/PR-/Her2+), and luminal loss (ER/PR loss from primary to metastasis). In the cohort of surgically resected metastases (n = 16), AR was expressed in 12 of 16 PBC and maintained in 11 of 12 corresponding MBCs. Of these, 36% showed stronger AR labeling in the metastases and none showed a decrease. In the cohort of metastases harvested at autopsy (n = 16), AR was expressed in 11 of 16 primary carcinomas and maintained in only 5 of 11 corresponding metastases. Of these, none showed increased AR and 80% showed decreased AR labeling. AR expression is overwhelmingly concordant between matched PBC and MBC at initial presentation. These findings validate AR as a therapeutic target in MBC and suggest that AR may need to be reevaluated in metastases even if the primary is negative. However, similar to ER/PR, AR expression is often decreased with a trend toward complete loss in end-stage metastases, suggesting a shift of AR expression between initial and end-stage metastases. This suggests an opportunity for targeted antiandrogen therapy at an earlier stage of disease progression.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hicks
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
authors.forename: Marc K
authors.initials: MK
authors.lastname: Halushka
authors.forename: John H
authors.initials: JH
authors.lastname: Fetting
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: Ben Ho
authors.initials: BH
authors.lastname: Park
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen