Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer

Urol Int. 2017;99(2):222-228. doi: 10.1159/000455158. Epub 2017 Jan 5.

Abstract

Objectives: To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors.

Materials and methods: Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients.

Results: In ADT treatment-naïve PCa patients, the AR expression was higher in tumor epithelial cells versus surrounding stromal cells (p < 0.001) and versus normal epithelium in the same patient (p = 0.043). The difference between tumoral AR expression and expression in normal epithelium was higher in patients with ≥15% of tumor cells with increased AR copy number (p = 0.019). Peritumoral stroma had lower AR expression in patients with lymph-node or distant metastases compared to those without metastases (p = 0.038).

Conclusions: This research evaluates the link between AR gene status, expression profile, and possible prognostic factors. Furthermore, it highlights the importance of the peritumoral environment in PCa. Additional research is needed to further clarify the role of stromal AR in PCa dissemination and identify possible therapeutic strategies to target this mechanism.

Keywords: Androgen receptor; Gene amplification; Prostate cancer; Protein expression; X chromosome.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Chromosomes, Human, X
  • DNA Copy Number Variations*
  • Epithelial Cells / chemistry
  • Epithelial Cells / pathology
  • Gene Dosage*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / analysis
  • Receptors, Androgen / genetics*
  • Stromal Cells / chemistry
  • Stromal Cells / pathology

Substances

  • AR protein, human
  • Biomarkers, Tumor
  • Receptors, Androgen