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Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications |
Pei Zhaoa,Yezi Zhua,Liang Chengb,*(),Jun Luoa,*()
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a Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA b Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA |
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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.
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Received: 31 May 2018
Available online: 28 September 2018
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Corresponding Authors:
Liang Cheng,Jun Luo
E-mail: liang_cheng@yahoo.com;jluo1@jhmi.edu
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Western blot of the full length androgen receptor (AR-FL) with androgen receptor C-terminal domain (AR-CTD) antibody and immunohistochemistry (IHC) staining of different AR isoforms in LNCaP95 and PC3 cell lines.
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Case | AR-V7 | AR CTD | SC-01 | 49.9% | 73.9% | SC-02 | 7.0% | 88.3% | SC-03 | 0.8% | 56.6% | SC-04 | 2.6% | 55.9% | SC-05 | Negative | 59.1% | SC-06 | Negative | 92.0% | SC-07 | Negative | 31.1% | SC-08 | Negative | 41.7% | SC-09 | Negative | 10.7% | SC-10 | Negative | Negative | SC-11 | Negative | Negative | SC-12 | Negative | Negative |
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Positive staining percentage of AR-V7 and AR-CTD IHC for 12 SCPC tissue specimens.
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Representative images of the immunohistochemistry staining (IHC) for androgen receptor C-terminal domain (AR-CTD) and androgen receptor splice variant-7 (AR-V7). (A) AR-CTD IHC for SC-01 (100× magnification); (B) AR-V7 IHC for SC-01 (100× magnification); (C) AR-CTD IHC for SC-01; (D) AR-V7 IHC for SC-01.
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