In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 191-191
Abstract:
191 Background: Previous studies have reported an association between blood-based detection of androgen receptor splice variant-7 (AR-V7) and resistance to abiraterone/enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). Further characterization of AR-V7 and its clinical correlates are necessary but depend on the development of methods that allow for reliable and specific measurement of AR-V7. In this study, we developed and evaluated a novel junction-specific AR-V7 RNA in situ hybridization (RISH) test. Methods: We developed a novel RISH assay targeting single exon-exon junction, allowing for highly-specific detection of mature cytoplasmic AR-FL and AR-V7 mRNA in native cell and tissue environment. We compared quantitative RISH AR-V7 results generated from an automated scoring system with AR-V7 levels quantified by RT-PCR in a panel of cell lines. Using the validated assay, we quantified AR-V7 signals in 58 prostate tumor biopsies. We conducted preliminary evaluation of the clinical correlates of AR-V7 detected. Results: The novel AR-V7 RISH test specifically detected mature cytoplasmic AR-V7 mRNA and did not detect nuclear pre-mRNA. AR-V7 RISH results were highly concordant with RT-PCR results. We generated quantitative AR-FL and AR-V7 data from 93.1% of the clinical specimens examined (54 of 58). Positive AR-V7 signals were detected in 23 specimens, all of which also co-expressed AR-FL. The median AR-V7/AR-FL ratio was 4.6%. Positive detection of AR-V7 was significantly correlated with prior treatment with second-line AR targeting agents and serum PSA ( p 〈 0.05), but not with any other baseline clinical variables. Notably, all castration-sensitive prostate cancer specimens (CSPC) (n = 9) were AR-V7 negative by this method. Association between AR-V7 and treatment outcome has yet to be fully evaluated. Conclusions: We demonstrate for the first time a highly specific and quantifiable AR-V7 RISH test for detection of clinically significant levels of AR-V7 mRNA in prostate tissue specimens. This test may be applied to liquid biopsy specimens to expand the utility. Prospective studies can be designed to evaluate the potential utility of this novel test in drug development and patient management.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.6_suppl.191
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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