Improving the Nuclear-Localized Androgen Receptor Splice Variant 7 Test

To the Editor We read with great interest the article by Scher et al. The aim of the study was to evaluate the clinical use of the Epic Sciences nuclear-localized androgen receptor splice variant 7 (AR-V7) test in circulating tumor cells (CTCs) to determine the best therapeutic strategy for patients with metastatic castration-resistant prostate cancer. The issue is interesting and addresses an important challenge of precision medicine. However, we would like to make a few remarks, which are mainly technical in nature. Although the assay used for analysis of the CTCs is highly sophisticated, we believe that the use of the fluorescence microscopy is a limiting factor that might directly affect results. Notably, the authors considered only AR-V7–positive CTCs exhibiting a nuclear-specific localization (according to AR-V7 scoring criteria) and discarded those with a diffuse signal. We believe that fluorescence analysis using confocal technology would be useful. Confocal microscopy allows determination with absolute certainty of the cellular localization of a protein through an assessment of its 3-dimensional organization. The use of confocal microscopy would have clarified the predictive value of hormone therapy of CTCs with both nuclear and cytoplasmic AR-V7 localization. Furthermore, the establishment of a cut-off value of AR-V7–positive CTCs would be appreciated for predictive purposes in the clinical setting.

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