AR-V7 Positivity Varies with Circulating Tumor Cell (CTC) Enrichment and Novel CTC Enrichment Is Able to Reduce AR-V7 False Positivity

Abstract

Background: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by RT-PCR shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflected contamination by hematopoietic cells. We tried a novel CTC enrichment instrument using Celsee® to clear hematopoietic cells. Methods: We tested whole blood or Celsee-enriched samples for AR-V7 by RT-PCR and included samples from 41 CRPC patients undergoing sequential therapy. We evaluated the associations between AR-V7 status and clinical factors. We evaluated factors affecting AR-V7 positivity. Results: AR-V7 positivity was lower in Celsee-enriched than in whole blood specimens. AR-V7 and clinical factors did not predict the therapy effectiveness. We found no significant differences in the effectiveness of Enz/Abi upon AR-V7 evaluation. All AR-V7 positive patients had resistance to Enz/Abi. DTX, CBZ, and Radium223 treatment showed no significant difference in the treatment effectiveness, regardless of AR-V7 presence. AR-V7 was more frequently positive than EOD2 in cases with bone metastases. Conclusion: Celsee® CTC enrichment suppresses the AR-V7 false positivity. All AR-V7 positive patients presented resistance to Enz/Abi. DTX, CBZ, and Radium223 were effective and remained treatment options. AR-V7 positivity should progressively appear in patients with advanced bone metastases.