Human androgen receptor expression in prostate cancer following androgen ablation

Eur Urol. 1997;31(1):1-6. doi: 10.1159/000474409.


Objective: Metastatic prostate cancer kills patients because their tumor cells fail to respond to combined androgen blockade (CAB) or respond and then relapse. To understand the molecular basis of androgen-insensitive growth of prostate tumor cells, we evaluated changes in human androgen receptor gene (hAR) mRNA levels in patients with prostate cancer treated with CAB.

Methods: The study was carried out using quantitative reverse-transcriptase polymerase chain reaction analysis. The level of hAR mRNA were compared to serum prostate-specific antigen and the mutant status of p53 in the tumor.

Results: hAR was expressed in 44 of 46 tumors from untreated patients, as opposed to 30 of 45 from those who had received CAB (p = 0.001). These 30 were from 8 of 9 stage D patients and from 22 of 36 patients on downsizing CAB therapy prior to radical prostatectomy. Expression was most often seen in high stages (56% of stage B vs. 89% of stage D) and high grades (52% of Gleason 3-7 vs. 92% of Gleason 8-10, p = 0.015). No tumor with a missense p53 mutation had hAR expression following CAB. Twenty-two patients following CAB were found to have undetectable serum prostate-specific antigen levels, while their tumor expressed hAR.

Conclusions: hAR expression after CAB is seen preferentially in high-grade, high-stage tumors, the type of prostate carcinomas that fail to have a durable remission. Undetectable serum prostate-specific antigen from tumors that remain hAR positive may predict relapse after hormonal ablative therapy.

MeSH terms

  • Androgen Antagonists / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Orchiectomy
  • Polymerase Chain Reaction
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / therapy*
  • RNA, Messenger / genetics
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Tumor Suppressor Protein p53 / metabolism


  • Androgen Antagonists
  • RNA, Messenger
  • Receptors, Androgen
  • Tumor Suppressor Protein p53
  • Prostate-Specific Antigen