A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer

A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer

Background: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by real-time polymerase chain reaction (RT-PCR) shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflects contamination by hema...

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Main Authors: Takehiko Nakasato, Chiho Kusaka, Mika Ota, Yuki Hasebe, Kumiko Ueda, Tsutomu Unoki, Kazuhiko Oshinomi, Jun Morita, Yoshiko Maeda, Takeshi Shichijo, Michio Naoe, Yoshio Ogawa
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Diagnostics
Subjects:
ar-v7
androgen receptors
docetaxel
cabazitaxel
abiraterone
enzalutamide
Online Access:https://www.mdpi.com/2075-4418/10/3/151
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spelling doaj-981f9ab19620412aa19f476041585af32020-11-25T03:10:05ZengMDPI AGDiagnostics2075-44182020-03-0110315110.3390/diagnostics10030151diagnostics10030151A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate CancerTakehiko Nakasato0Chiho Kusaka1Mika Ota2Yuki Hasebe3Kumiko Ueda4Tsutomu Unoki5Kazuhiko Oshinomi6Jun Morita7Yoshiko Maeda8Takeshi Shichijo9Michio Naoe10Yoshio Ogawa11Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanBackground: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by real-time polymerase chain reaction (RT-PCR) shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflects contamination by hematopoietic cells. We tried a novel circulating tumor cell (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 enzalutamide/abiraterone (Enz/Abi) upon AR-V7 evaluation. All AR-V7 positive patients had resistance to Enz/Abi. Docetaxel (DTX), cabazitaxel (CBZ), and Radium223 treatment showed no significant difference in the treatment effectiveness, regardless of AR-V7 presence. AR-V7 was more frequently positive than Extent of disease (EOD) 2 in cases with bone metastases. Conclusion: Celsee CTC enrichment suppresses AR-V7 false positivity. All AR-V7 positive patients presented resistance to Enz/Abi. DTX, CBZ, and Radium223 were effective and remain treatment options. AR-V7 positivity should progressively appear in patients with advanced bone metastases.https://www.mdpi.com/2075-4418/10/3/151ar-v7androgen receptorsdocetaxelcabazitaxelabirateroneenzalutamide
collection DOAJ
language English
format Article
sources DOAJ
author Takehiko Nakasato
Chiho Kusaka
Mika Ota
Yuki Hasebe
Kumiko Ueda
Tsutomu Unoki
Kazuhiko Oshinomi
Jun Morita
Yoshiko Maeda
Takeshi Shichijo
Michio Naoe
Yoshio Ogawa
spellingShingle Takehiko Nakasato
Chiho Kusaka
Mika Ota
Yuki Hasebe
Kumiko Ueda
Tsutomu Unoki
Kazuhiko Oshinomi
Jun Morita
Yoshiko Maeda
Takeshi Shichijo
Michio Naoe
Yoshio Ogawa
A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer
Diagnostics
ar-v7
androgen receptors
docetaxel
cabazitaxel
abiraterone
enzalutamide
author_facet Takehiko Nakasato
Chiho Kusaka
Mika Ota
Yuki Hasebe
Kumiko Ueda
Tsutomu Unoki
Kazuhiko Oshinomi
Jun Morita
Yoshiko Maeda
Takeshi Shichijo
Michio Naoe
Yoshio Ogawa
author_sort Takehiko Nakasato
title A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer
title_short A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer
title_full A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer
title_fullStr A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer
title_full_unstemmed A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer
title_sort novel, circulating tumor cell enrichment method reduces arv7 false positivity in patients with castration-resistant prostate cancer
publisher MDPI AG
series Diagnostics
issn 2075-4418
publishDate 2020-03-01
description Background: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by real-time polymerase chain reaction (RT-PCR) shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflects contamination by hematopoietic cells. We tried a novel circulating tumor cell (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 enzalutamide/abiraterone (Enz/Abi) upon AR-V7 evaluation. All AR-V7 positive patients had resistance to Enz/Abi. Docetaxel (DTX), cabazitaxel (CBZ), and Radium223 treatment showed no significant difference in the treatment effectiveness, regardless of AR-V7 presence. AR-V7 was more frequently positive than Extent of disease (EOD) 2 in cases with bone metastases. Conclusion: Celsee CTC enrichment suppresses AR-V7 false positivity. All AR-V7 positive patients presented resistance to Enz/Abi. DTX, CBZ, and Radium223 were effective and remain treatment options. AR-V7 positivity should progressively appear in patients with advanced bone metastases.
topic ar-v7
androgen receptors
docetaxel
cabazitaxel
abiraterone
enzalutamide
url https://www.mdpi.com/2075-4418/10/3/151
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