To the Editor We read with great interest the article by Scher et al.1 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.2 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.
Nicolazzo C, Gradilone A, Gazzaniga P. Improving the Nuclear-Localized Androgen Receptor Splice Variant 7 Test. JAMA Oncol. 2019;5(3):433–434. doi:10.1001/jamaoncol.2018.6683
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