Table of Contents
Definition / general | Essential features | Pathophysiology | Diagnosis | Clinical features | Uses by pathologists | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Johnson G, Roychowdhury M. Androgen receptor (AR). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsar.html. Accessed December 25th, 2024.
Definition / general
- Androgen receptor (AR) is a member of the superfamily of ligand responsive transcription regulators
- It functions in the nucleus where it is believed to act as a transcriptional regulator mediating the action of androgens
- 918 amino acid protein encoded by a single copy gene on X q11 - q12
Essential features
- Expressed variably by both ER / PR+ as well as ER / PR- breast cancers
- Most useful for triple negative breast cancer, luminal androgen subtype
- Detected by IHC or gene classifier (molecular testing)
- Predicts favorable prognosis in early stage disease based on current studies, some controversy exists
- Ongoing trials to study the effect of androgen receptor targeted therapy in
- AR+ triple negative breast cancer
- Hormone receptor positive metastatic breast cancer
- HER2+ metastatic breast cancer
Pathophysiology
- Expressed in two types of mammary epithelial cells:
- Metaplastic apocrine cells (lack ER / PR)
- Luminal epithelial cells (5 - 30%) (co-expressed with ER / PR)
Diagnosis
- May be detected by gene classifier or IHC
- Any nuclear IHC staining in tumor cells is considered as positive result but further subdivided into subgroups with 1 - 10% and > 10% positive staining
Clinical features
- Expressed variably depending on tumor subtype:
- ER+ breast tumors: 67 - 88%
- All molecular apocrine tumors
- 12 - 50% of ER- classic invasive ductal carcinoma
- Triple negative breast tumors: 6.6 - 75%; range due to variable cutoffs, source of antibody and methodologies, highest expression in luminal androgen receptor subtype (Breast Cancer Res Treat 2011;130:477, Clin Cancer Res 2011;17:1867, Clin Cancer Res 2013;19:5505, Clin Adv Hematol Oncol 2016;14:186)
- Predicts favorable prognosis based on some studies, however controversy exists
Uses by pathologists
- Apocrine marker
- Breast carcinoma marker helpful in determining primary site of metastases
- Paget disease marker
- Sebaceous carcinoma marker; may help differentiate from squamous cell and basal cell carcinomas (Am J Clin Pathol 2010;134:22)
Treatment
- In addition to neoadjuvant chemotherapy, patients with AR+ tumors may benefit from AR targeted therapies such as bicalutamide (AR antagonist) or enzalutamide (AR inhibitor) (ascopost: Targeting the Androgen Receptor in Breast Cancer [Accessed 8 May, 2018])
- Newer therapies are underway
Microscopic (histologic) description
- Nuclear stain in tumor cells is quantified
Microscopic (histologic) images
Contributed by Monika Roychowdhury, M.D.
Case #214
Images hosted on other servers:
Positive staining - normal
- Skin apocrine and sebaceous glands (J Invest Dermatol 1991;97:264), prostate basal cells (J Steroid Biochem Mol Biol 1992;41:693)
- Early male and female fetal gonads (Hum Reprod 2004;19:1659)
- Also oral mucosa
Positive staining - disease
- Breast: apocrine metaplasia (100%, J Clin Pathol 1999;52:838) apocrine DCIS (J Clin Pathol 2002;55:14) apocrine carcinoma (Jpn J Clin Oncol 2012;42:375, Case Rep Pathol 2013;2013:170918), cystic hypersecretory DCIS (Histopathology 2005;46:43), high grade DCIS, high grade invasive breast carcinoma (primary and metastatic), mammary and extramammary Paget disease (Mod Pathol 2005;18:1283), PASH spindle cells (Int J Clin Exp Pathol 2009;3:87), sebaceous carcinoma, tall cell-like tumors (Int J Surg Pathol 2006;14:79)
- Associated with better prognosis in all types of breast cancer, and better overall survival in ER+ tumors (PLoS One 2013;8:e82650)
- Nasal cavity: nasopharyngeal angiofibroma (75%, Mod Pathol 1998;11:1122, stromal cells in 38% Am J Clin Pathol 2006;125:832)
- Ovary: serous tumors (50%), Sertoli-Leydig tumor (Hum Pathol 1997;28:1206), ovarian surface epithelium (higher AR staining in patients with cervical squamous cell carcinoma, J Ovarian Res 2013;6:85)
- Salivary glands: giant cell tumor, salivary duct carcinomas (Am J Clin Pathol 2003;119:801)
- Skin: Paget disease, sebaceous carcinoma (Am J Clin Pathol 2010;134:22)
- Soft tissue: desmoid tumor (53%, Tohoku J Exp Med 2006;210:189), spindle cell lipoma in men and most women (Arch Pathol Lab Med 2008;132:81)
- Uterus: adenosarcoma (35%), endometrial polyp with atypical features, endometrial stromal nodule, endometrium in polycystic ovarian syndrome. (Biol Reprod 2002;66:297), leiomyosarcoma (variable, Cancer 2004;101:1455, Tumour Biol 2011;32:451)
Negative staining
- Neuroendocrine cells
- Adenomatoid tumor, BRCA1 breast carcinoma, breast fibromatosis (Arch Pathol Lab Med 2000;124:276)
Additional references
Board review style question #1
Androgen receptor testing is most useful in:
- ER+, PR+, HER2+ breast tumor
- ER+, PR+, HER2- breast tumor
- ER-, PR-, HER2+ breast tumor
- ER-, PR-, HER2- breast tumor
Board review style answer #1