Urology, University of Muenster Medical Center, Muenster, Germany.
Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
BJU Int. 2018 Aug;122(2):219-226. doi: 10.1111/bju.14146. Epub 2018 Feb 14.
To compare the performance of two established androgen receptor splice variant 7 (AR-V7) mRNA detection systems, as paradoxical responses to next-generation androgen-deprivation therapy in AR-V7 mRNA-positive circulating tumour cells (CTC) of patients with castration-resistant prostate cancer (CRPC) could be related to false-positive classification using detection systems with different sensitivities.
We compared the performance of two established mRNA-based AR-V7 detection technologies using either SYBR Green or TaqMan chemistries. We assessed in vitro performance using eight genitourinary cancer cell lines and serial dilutions in three AR-V7-positive prostate cancer cell lines, as well as in 32 blood samples from patients with CRPC.
Both assays performed identically in the cell lines and serial dilutions showed identical diagnostic thresholds. Performance comparison in 32 clinical patient samples showed perfect concordance between the assays. In particular, both assays determined AR-V7 mRNA-positive CTCs in three patients with unexpected responses to next-generation anti-androgen therapy. Thus, technical differences between the assays can be excluded as the underlying reason for the unexpected responses to next-generation anti-androgen therapy in a subset of AR-V7 patients.
Irrespective of the method used, patients with AR-V7 mRNA-positive CRPC should not be systematically precluded from an otherwise safe treatment option.
比较两种已建立的雄激素受体剪接变异体 7 (AR-V7) mRNA 检测系统的性能,因为在接受抗雄激素治疗的 AR-V7 mRNA 阳性循环肿瘤细胞(CTC)中存在矛盾的反应,这可能与使用敏感性不同的检测系统进行假阳性分类有关。
我们使用 SYBR Green 或 TaqMan 化学方法比较了两种已建立的基于 mRNA 的 AR-V7 检测技术的性能。我们使用 8 种泌尿生殖系统癌细胞系和 3 种 AR-V7 阳性前列腺癌细胞系的系列稀释液评估了体外性能,还评估了 32 例去势抵抗性前列腺癌(CRPC)患者的 32 个血液样本。
两种检测方法在细胞系和系列稀释液中的性能完全相同,均显示出相同的诊断阈值。在 32 例临床患者样本中的性能比较显示,两种检测方法具有完美的一致性。特别是,两种检测方法均在 3 名接受新一代抗雄激素治疗的患者中检测到了 AR-V7 mRNA 阳性 CTC。因此,检测方法之间的技术差异可以排除作为新一代抗雄激素治疗在部分 AR-V7 患者中出现意外反应的潜在原因。
无论使用哪种方法,不应将 AR-V7 mRNA 阳性 CRPC 患者系统地排除在安全的治疗选择之外。