Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications

Pei Zhao, Yezi Zhu, Liang Cheng, Jun Luo

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)109-113
Number of pages5
JournalAsian Journal of Urology
Volume6
Issue number1
DOIs
StatePublished - Jan 2019

Fingerprint

Small Cell Carcinoma
Androgen Receptors
Prostate
Therapeutics
Staining and Labeling
Prostate-Specific Antigen
Androgens
Prostatic Neoplasms
Circulating Neoplastic Cells

Keywords

  • Androgen receptor
  • Androgen receptor splice variant-7
  • Immunohistochemistry
  • Small cell prostate carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

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.

In: Asian Journal of Urology, Vol. 6, No. 1, 01.2019, p. 109-113.

Research output: Contribution to journalArticle

@article{e44a0b89d9de42bdb4ff247ef62bcaa6,
title = "Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications",
abstract = "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.",
keywords = "Androgen receptor, Androgen receptor splice variant-7, Immunohistochemistry, Small cell prostate carcinoma",
author = "Pei Zhao and Yezi Zhu and Liang Cheng and Jun Luo",
year = "2019",
month = "1",
doi = "10.1016/j.ajur.2018.09.003",
language = "English (US)",
volume = "6",
pages = "109--113",
journal = "Asian Journal of Urology",
issn = "2214-3882",
publisher = "Elsevier (Singapore) Pte Ltd",
number = "1",

}

TY - JOUR

T1 - Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma

T2 - Diagnostic and therapeutic implications

AU - Zhao, Pei

AU - Zhu, Yezi

AU - Cheng, Liang

AU - Luo, Jun

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Androgen receptor

KW - Androgen receptor splice variant-7

KW - Immunohistochemistry

KW - Small cell prostate carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85070756965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070756965&partnerID=8YFLogxK

U2 - 10.1016/j.ajur.2018.09.003

DO - 10.1016/j.ajur.2018.09.003

M3 - Article

AN - SCOPUS:85070756965

VL - 6

SP - 109

EP - 113

JO - Asian Journal of Urology

JF - Asian Journal of Urology

SN - 2214-3882

IS - 1

ER -