Synapse - Immunohistochemistry-based assessment of androgen receptor status and the AR-null phenotype in metastatic castrate resistant prostate cancer

Immunohistochemistry-based assessment of androgen receptor status and the AR-null phenotype in metastatic castrate resistant prostate cancer Journal Article

Authors:	Gupta, S.; Vanderbilt, C.; Abida, W.; Fine, S. W.; Tickoo, S. K.; Al-Ahmadie, H. A.; Chen, Y. B.; Sirintrapun, S. J.; Chadalavada, K.; Nanjangud, G. J.; Bialik, A.; Morris, M. J.; Scher, H. I.; Ladanyi, M.; Reuter, V. E.; Gopalan, A.
Article Title:	Immunohistochemistry-based assessment of androgen receptor status and the AR-null phenotype in metastatic castrate resistant prostate cancer
Abstract:	Background: Molecular and immunohistochemistry-based profiling of prostatic adenocarcinoma has revealed frequent Androgen Receptor (AR) gene and protein alterations in metastatic disease. This includes an AR-null non-neuroendocrine phenotype of metastatic castrate resistant prostate cancer which may be less sensitive to androgen receptor signaling inhibitors. This AR-null non-neuroendocrine phenotype is thought to be associated with TP53 and RB1 alterations. Herein, we have correlated molecular profiling of metastatic castrate resistant prostate cancer with AR/P53/RB immunohistochemistry and relevant clinical correlates. Design: Twenty-seven cases of metastatic castrate resistant prostate cancer were evaluated using histopathologic examination to rule out neuroendocrine differentiation. A combination of a hybridization exon-capture next-generation sequencing-based assay (n = 26), fluorescence in situ hybridization for AR copy number status (n = 16), and immunohistochemistry for AR (n = 27), P53 (n = 24) and RB (n = 25) was used to profile these cases. Results: Of 27 metastatic castrate resistant prostate cancer cases, 17 had AR amplification and showed positive nuclear expression of AR by immunohistochemistry. Nine cases lacked AR copy number alterations using next-generation sequencing/fluorescence in situ hybridization. A subset of these metastatic castrate resistant prostate cancer cases demonstrated the AR-null phenotype by immunohistochemistry (five cases and one additional case where next-generation sequencing failed). Common co-alterations in these cases involved the TP53, RB1, and PTEN genes and all these patients received prior therapy with androgen receptor signaling inhibitors (abiraterone and/or enzalutamide). Conclusions: Our study suggests that AR immunohistochemistry may distinguish AR-null from AR-expressing cases in the metastatic setting. AR-null status informs clinical decision-making regarding continuation of therapy with androgen receptor signaling inhibitors and consideration of other treatment options. This might be a relevant and cost-effective diagnostic strategy when there is limited access and/or limited tumor material for molecular testing. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Journal Title:	Prostate Cancer and Prostatic Diseases
Volume:	23
Issue:	3
ISSN:	1365-7852
Publisher:	Nature Publishing Group
Date Published:	2020-09-01
Start Page:	507
End Page:	516
Language:	English
DOI:	10.1038/s41391-020-0214-6
PUBMED:	32094488
PROVIDER:	scopus
PMCID:	PMC7433029
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079765608&doi=10.1038%2fs41391-020-0214-6&partnerID=40&md5=5d18d2a7c91b2e0865e130c59fdadebb
Notes:	Article -- Source: Scopus