AR-V7 Protein Expression in Circulating Tumour Cells Is Not Predictive of Treatment Response in mCRPC

Urol Int. 2020;104(3-4):253-262. doi: 10.1159/000504416. Epub 2020 Jan 17.

Abstract

Introduction: Androgen receptor variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC) and has shown potential as a predictive biomarker in circulating tumour cells (CTCs) isolated from the bloodstream in terms of a liquid biopsy. Studies have shown that AR-V7 is a potential surrogate for selecting drug classes for systemic treatment by detecting nuclear AR-V7 by immunofluorescence or measuring AR-V7 messenger RNA by quantitative PCR. Here, we assessed the predictive value of AR-V7 detected by classical immunohistochemistry (IHC) for treatment response.

Methods: CTCs were isolated by cell separation by density gradient centrifugation from patients with metastatic CRPC (n = 26) before, while, and after undergoing a new therapy with chemotherapy (cabazitaxel or docetaxel) or antiandrogen (enzalutamide or abiraterone). CTCs were sequentially cytospun on object slides, and AR-V7 status was then detected by IHC based on a staining regime established on a 22Rv1 cell line with antibodies against CK8/18 und AR-V7.

Results: AR-V7 status detected by IHC showed no predictive value for progression-free survival (PFS). Kaplan-Meier analysis revealed that there was no difference in PFS between patients found positive or negative for AR-V7.

Discussion/conclusion: AR-V7 detected by classical IHC has no predictive value for treatment response in the described setting. The future role of AR-V7 in CTCs as a biomarker in clinical routine remains elusive.

Keywords: AR-V7; Abiraterone; Androgen receptor; Circulating tumour cells; Docetaxel; Enzalutamide.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Docetaxel / therapeutic use*
  • Humans
  • Male
  • Neoplastic Cells, Circulating / metabolism*
  • Prognosis
  • Prospective Studies
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / metabolism*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Receptors, Androgen / biosynthesis*
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • AR protein, human
  • Androgen Antagonists
  • Antineoplastic Agents
  • Receptors, Androgen
  • Taxoids
  • Docetaxel
  • cabazitaxel