MP6-11 A NOVEL BLOOD-BASED ASSAY FOR DETECTING ANDROGEN RECEPTOR SPLICE VARIANTS IN PATIENTS WITH ADVANCED PROSTATE CANCER

purpose of this study was to determine the tissue specific expression, co-localization, and ratio of AR and ARv7 in normal and hormonenaive PCa. METHODS: Antibodies to detect full length AR and ARv7 were used on hormone-naive tumor-adjacent normal prostate, high-grade intraepithelial neoplasia (HGPIN), primary PCa samples, and metastases (Mets). Tissue specific protein expression and co-localization of AR and ARv7 were quantified using multispectral imaging technology. Ratios of AR and ARv7 were determined. RESULTS: AR and ARv7 were observed in nuclei of stromal and epithelial cells from all normal and pathologic specimens. In epithelial tissue, nuclear expression of ARv7 was significantly increased in HGPIN and Mets compared to normal prostate, but not PCa. Expression of AR was increased in PCa and Mets but not HGPIN. The proportion of double negative (AR-/ARv7-) cells was lower in HGPIN, PCa, and Mets compared to normal prostate. The proportion of single positive AR-/ARv7þ was higher in HGPIN and the number of single positive ARþ/ARv7cells was higher in PCa. Double positive ARþ/ ARv7þ cells were more abundant in Mets. In stromal tissues, expression of ARv7 was increased in HGPIN and Mets, but not PCa. Expression of AR was similar in HGPIN and PCa compared to normal prostate, but AR was significantly higher in Mets. The number of double negative AR-/ARv7cells was lower in HGPIN and Mets. Single positive AR-/ARv7þ cells were increased in HGPIN. No changes were found in single positive ARþ/ARv7cells. The proportion of double positive ARþ/ARv7þ cells was higher in Mets than normal tissue. The epithelial ratio of ARv7:AR was significantly higher in PCa than normal prostate tissue (p1⁄40.0003) but not HGPIN (p1⁄40.99) or Mets (p1⁄40.57). In the stroma, the ratio of ARv7:AR was higher in HGPIN (p1⁄40.02) but not PCa (p>0.99) or Mets (p>0.99). CONCLUSIONS: ARv7 is expressed in both the epithelia and stroma during early stages of prostate cancer, and expression of ARv7 is increased in HGPIN in the absence of changes in AR expression. These data support a potential role of ARv7 signaling in early stages of prostate cancer development.