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
N1 - Funding Information:
The work at Johns Hopkins University School of Medicine was supported by National Institutes of Health Grants ( R01 CA185297 and P30 CA006973 ), Department of Defense Prostate Cancer Research Program Grants ( W81XWH-15-2-0050 ), Johns Hopkins Prostate SPORE Grant ( P50 CA058236 ), and the Prostate Cancer Foundation . This paper is dedicated to the memory of Donald S. Coffey.
Funding Information:
The work at Johns Hopkins University School of Medicine was supported by National Institutes of Health Grants (R01 CA185297 and P30 CA006973), Department of Defense Prostate Cancer Research Program Grants (W81XWH-15-2-0050), Johns Hopkins Prostate SPORE Grant (P50 CA058236), and the Prostate Cancer Foundation. This paper is dedicated to the memory of Donald S. Coffey.
Publisher Copyright:
© 2019 Editorial Office of Asian Journal of Urology
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
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U2 - 10.1016/j.ajur.2018.09.003
DO - 10.1016/j.ajur.2018.09.003
M3 - Article
C2 - 30775254
AN - SCOPUS:85070756965
SN - 2214-3882
VL - 6
SP - 109
EP - 113
JO - Asian Journal of Urology
JF - Asian Journal of Urology
IS - 1
ER -