HUMAN ANDROGEN RECEPTOR EXPRESSION IN PROSTATE-CANCER FOLLOWING ANDROGEN ABLATION

Objective: Metastatic prostate cancer kills patients because their tum or cells fail to respond to combined androgen blockade (CAB) or respon d and then relapse. To understand the molecular basis of androgen-inse nsitive growth of prostate tumor cells, we evaluated changes in human androgen receptor gene (hAR) mRNA levels in patients with prostate can cer treated with CAB. Methods: The study was carried out using quantit ative reverse-transcriptase polymerase chain reaction analysis. The le vels of hAR mRNA were compared to serum prostate-specific antigen and the mutant status of p53 in the tumor. Results: hAR was expressed in 4 4 of 46 tumors from untreated patients, as opposed to 30 of 45 from th ose 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 stage s (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 followi ng 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. Un detectable serum prostate-specific antigen from tumors that remain hAR positive may predict relapse after hormonal ablative therapy.