Human androgen receptor expression in prostate cancer following androgen ablation

R. De vere White, F. Meyers, S. G. Chi, S. Chamberlain, D. Siders, F. Lee, S. Stewart, P. H. Gumerlock

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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 levels 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.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalEuropean Urology
Volume31
Issue number1
DOIs
Publication statusPublished - 1997
Externally publishedYes

Keywords

  • Complete androgen blockade
  • Hormones
  • Human androgen receptor
  • Prostate cancer
  • Reverse-transcriptase polymerase chain reaction

ASJC Scopus subject areas

  • Urology

Fingerprint Dive into the research topics of 'Human androgen receptor expression in prostate cancer following androgen ablation'. Together they form a unique fingerprint.

Cite this