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Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications
OBJECTIVE: Small cell prostate carcinoma (SCPC) is a rare and highly malignant subtype of prostate cancer. SCPC frequently lacks androgen receptor (AR) and prostate-specific antigen (PSA) expression, and often responds poorly to androgen deprivation therapy (ADT). AR splice variant-7 (AR-V7) is a tr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Second Military Medical University
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363596/ https://www.ncbi.nlm.nih.gov/pubmed/30775254 http://dx.doi.org/10.1016/j.ajur.2018.09.003 |
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author | Zhao, Pei Zhu, Yezi Cheng, Liang Luo, Jun |
author_facet | Zhao, Pei Zhu, Yezi Cheng, Liang Luo, Jun |
author_sort | Zhao, Pei |
collection | PubMed |
description | OBJECTIVE: Small cell prostate carcinoma (SCPC) is a rare and highly malignant subtype of prostate cancer. SCPC frequently lacks androgen receptor (AR) and prostate-specific antigen (PSA) expression, and often responds poorly to androgen deprivation therapy (ADT). AR splice variant-7 (AR-V7) is a truncated AR protein implicated in resistance to AR-targeting therapies. AR-V7 expression in castration-resistant prostate cancers has been evaluated extensively, and blood-based detection of AR-V7 has been associated with lack of response to abiraterone and enzalutamide. However, whether AR-V7 is expressed in SCPC is not known. METHODS: Using validated antibodies, we performed immunohistochemistry (IHC) assay for the full-length AR (AR-FL) and (AR-V7) on post-ADT surgical SCPC specimens. RESULTS: Seventy-five percent (9/12) of the specimens showed positive staining for the AR-FL with various intensities. Thirty-three percent (4/12) of the specimens showed positive staining for AR-V7. Among the specimens with positive AR-V7 staining, two samples displayed very weak staining, one sample showed weak-to-moderate staining, and one sample showed strong staining. All positive specimens displayed a heterogeneous pattern of AR-FL/AR-V7 staining. All specimens positive for AR-V7 were also positive for AR-FL. CONCLUSION: The study findings support the existence of measurable AR-FL and AR-V7 proteins in SCPC specimens. The results also have implications in detection of AR-V7 in specimens obtained through systemic sampling approaches such as circulating tumor cells. A positive AR-V7 finding by blood-based tests is not impossible in patients with SCPC who often demonstrate low PSA values. |
format | Online Article Text |
id | pubmed-6363596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Second Military Medical University |
record_format | MEDLINE/PubMed |
spelling | pubmed-63635962019-02-15 Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications Zhao, Pei Zhu, Yezi Cheng, Liang Luo, Jun Asian J Urol Original Article OBJECTIVE: Small cell prostate carcinoma (SCPC) is a rare and highly malignant subtype of prostate cancer. SCPC frequently lacks androgen receptor (AR) and prostate-specific antigen (PSA) expression, and often responds poorly to androgen deprivation therapy (ADT). AR splice variant-7 (AR-V7) is a truncated AR protein implicated in resistance to AR-targeting therapies. AR-V7 expression in castration-resistant prostate cancers has been evaluated extensively, and blood-based detection of AR-V7 has been associated with lack of response to abiraterone and enzalutamide. However, whether AR-V7 is expressed in SCPC is not known. METHODS: Using validated antibodies, we performed immunohistochemistry (IHC) assay for the full-length AR (AR-FL) and (AR-V7) on post-ADT surgical SCPC specimens. RESULTS: Seventy-five percent (9/12) of the specimens showed positive staining for the AR-FL with various intensities. Thirty-three percent (4/12) of the specimens showed positive staining for AR-V7. Among the specimens with positive AR-V7 staining, two samples displayed very weak staining, one sample showed weak-to-moderate staining, and one sample showed strong staining. All positive specimens displayed a heterogeneous pattern of AR-FL/AR-V7 staining. All specimens positive for AR-V7 were also positive for AR-FL. CONCLUSION: The study findings support the existence of measurable AR-FL and AR-V7 proteins in SCPC specimens. The results also have implications in detection of AR-V7 in specimens obtained through systemic sampling approaches such as circulating tumor cells. A positive AR-V7 finding by blood-based tests is not impossible in patients with SCPC who often demonstrate low PSA values. Second Military Medical University 2019-01 2018-09-28 /pmc/articles/PMC6363596/ /pubmed/30775254 http://dx.doi.org/10.1016/j.ajur.2018.09.003 Text en © 2019 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Zhao, Pei Zhu, Yezi Cheng, Liang Luo, Jun Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications |
title | Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications |
title_full | Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications |
title_fullStr | Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications |
title_full_unstemmed | Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications |
title_short | Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications |
title_sort | detection of androgen receptor (ar) and ar-v7 in small cell prostate carcinoma: diagnostic and therapeutic implications |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363596/ https://www.ncbi.nlm.nih.gov/pubmed/30775254 http://dx.doi.org/10.1016/j.ajur.2018.09.003 |
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