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J Urol. 2016 Dec;196(6):1758-1763. doi: 10.1016/j.juro.2016.06.095. Epub 2016 Jul 20.

A Whole Blood Assay for AR-V7 and ARv567es in Patients with Prostate Cancer.

Author information

1
Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana.
2
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana; Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana.
3
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana.
4
Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana.
5
Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address: hzhang@tulane.edu.

Abstract

PURPOSE:

Most prostate cancer mortality can be attributed to metastatic castration resistant prostate cancer, an advanced stage that remains incurable despite recent advances. The AR (androgen receptor) signaling axis remains active in castration resistant prostate cancer. Recent studies suggest that expression of the AR-V (AR splice variant) AR-V7 may underlie resistance to abiraterone and enzalutamide. However, controversy exists over the optimal assay. Our objective was to develop a fast and sensitive assay for AR-Vs in patients.

MATERIALS AND METHODS:

Two approaches were assessed in this study. The first approach was based on depletion of leukocytes and the second one used RNA purified directly from whole blood preserved in PAXgene® tubes. Transcript expression was analyzed by quantitative reverse transcription-polymerase chain reaction.

RESULTS:

Through a side-by-side comparison we found that the whole blood approach was suitable to detect AR-Vs. The specificity of the assay was corroborated in a cancer-free cohort. Using the PAXgene assay samples from a cohort of 46 patients with castration resistant prostate cancer were analyzed. Overall, AR-V7 and ARv567es were detected in 67.53% and 29.87% of samples, respectively. Statistical analysis revealed a strong association of AR-V positivity with a history of second line hormonal therapies.

CONCLUSIONS:

To our knowledge this is the first study to demonstrate that PAXgene preserved whole blood can be used to obtain clinically relevant information regarding the expression of 2 AR-Vs. These data on a castration resistant prostate cancer cohort support a role for AR-Vs in resistance to therapies targeting the AR ligand-binding domain.

KEYWORDS:

androgen; biomarkers; blood; prostatic neoplasms; protein isoforms; receptors; tumor

PMID:
27449259
PMCID:
PMC5161406
DOI:
10.1016/j.juro.2016.06.095
[Indexed for MEDLINE]
Free PMC Article

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