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Performance comparison of two androgen receptor splice variant 7 (AR-V7) detection methods
Christof Bernemann1, Julie Steinestel1, Verena Humberg1
1Urology, University of Muenster Medical Center, Muenster, Germany.
BJU International
|January 24, 2018
Summary
Two androgen receptor splice variant 7 (AR-V7) mRNA detection systems showed identical performance in identifying AR-V7 mRNA-positive circulating tumor cells (CTCs) in prostate cancer patients. Technical assay differences do not explain unexpected treatment responses.
Area of Science:
- Oncology
- Molecular Diagnostics
Background:
- Castration-resistant prostate cancer (CRPC) treatment response can be influenced by androgen receptor splice variant 7 (AR-V7) mRNA expression.
- Paradoxical responses to novel androgen-deprivation therapies in AR-V7 mRNA-positive patients warrant investigation into detection system accuracy.
Purpose of the Study:
- To compare the diagnostic performance of two established mRNA-based AR-V7 detection systems.
- To determine if assay variability contributes to unexpected treatment outcomes in CRPC patients.
Main Methods:
- Two AR-V7 mRNA detection assays utilizing SYBR Green and TaqMan chemistries were compared.
- In vitro analysis included eight genitourinary cancer cell lines and serial dilutions of AR-V7 positive cell lines.
- Clinical validation involved analyzing 32 blood samples from CRPC patients for AR-V7 mRNA-positive circulating tumor cells (CTCs).
Main Results:
- Both AR-V7 mRNA detection assays demonstrated identical performance in cell lines and serial dilutions, establishing consistent diagnostic thresholds.
- Perfect concordance was observed between the two assays when analyzing 32 clinical CRPC patient samples.
- Both assays identified AR-V7 mRNA-positive CTCs in three patients exhibiting unexpected responses to next-generation anti-androgen therapy.
Conclusions:
- Technical variations between the evaluated AR-V7 mRNA detection systems are not the cause of unexpected treatment responses in a subset of CRPC patients.
- Patients with AR-V7 mRNA-positive CRPC should not be excluded from potentially beneficial and safe treatment options based solely on AR-V7 status.
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