Abstract 2640: Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma by immunohistochemistry

Abstract

Abstract Background: Small cell prostate carcinoma (SCPC) is a rare and highly malignant subtype of prostate cancer. SCPC only accounts for 0.5%-2% of untreated primary prostate cancer, but can present in up to 25% lethal metastatic prostate cancer autopsies. Small cell prostate carcinoma frequently lacks androgen receptor (AR) and prostate specific antigen (PSA) expression, and often responds poorly to androgen deprivation therapy (ADT). However, the expression pattern of different AR isoforms in SCPC after ADT remains poorly characterized. In this study, we have validated and developed a new immunohistochemical assay for full length AR (AR-FL) and AR splice variant-7 (AR-V7) protein expression in prostate cancer specimens. The expression of AR-FL and AR-V7 protein were determined in post-ADT radical prostatectomy samples from twelve SCPC patients. In this study, we developed and validated a new immunohistochemical assay for the full-length AR (AR-FL) and AR splice variant-7 (AR-V7) proteins. We conducted an IHC study in post-ADT surgical specimens from twelve SCPC patients treated with neoadjuvant ADT. Methods: AR-FL, AR-V7, and total AR proteins were specifically detected using AR C-terminal domain antibody (Sigma-Aldrich), AR-V7 antibody (RevMab), and AR N-terminal domain antibody (AR441, Santa Cruz), respectively. These antibodies were validated using prostate cancer cell lines with known AR profiles, including LNCaP95 cells which express both AR-FL and AR-V7 and the AR-negative PC3 cells. The IHC protocols were optimized for each individual antibody, and applied to the 12 SC/NE tissue specimens. Results: Twelve surgical (RP or TURP) prostate small cell carcinoma specimens were collected from patients after neoadjuvant hormonal therapy at Indiana University School of Medicine. Seventy five percent (9/12) of the specimens showed positive staining for the full-length AR 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/AR-V7 staining. All specimens positive for AR-V7 were also positive for the full length AR. Conclusion and future direction: Our preliminary results indicate that small cell prostate carcinoma may continue to express AR and AR-V7. The functional and clinical relevance of AR/AR-V7 detection in this setting remains unknown. Future investigation will focus on clinical correlation in an expanded patient cohort. Citation Format: Pei Zhao, Yezi Zhu, Liang Cheng, Jun Luo. Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma by immunohistochemistry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2640.