Human androgen receptor expression in prostate cancer following androgen ablation

Ralph W deVere White, Frederick J Meyers, S. G. Chi, S. Chamberlain, D. Siders, F. Lee, Susan L Stewart, P. H. Gumerlock

Research output: Contribution to journalArticle

62 Scopus citations

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 (US)
Pages (from-to)1-6
Number of pages6
JournalEuropean Urology
Volume31
Issue number1
StatePublished - 1997

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Keywords

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

ASJC Scopus subject areas

  • Urology

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