Differential alterations in 5α-reductase type 1 and type 2 levels during development and progression of prostate cancer

• Published in: The Prostate Vol. 63; no. 3; pp. 231 - 239
• Main Authors: Thomas, Lynn N., Lazier, C.B., Gupta, R., Norman, R.W., Troyer, D.A., O'Brien, S.P., Rittmaster, R.S.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.05.2005
• Subjects: 5α-reductase inhibitors; androgens; BPH; immunohistochemistry; PIN
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20188

BACKGROUND In the prostate, conversion of testosterone to dihydrotestosterone (DHT), by the enzymes 5α‐reductase types 1 and 2 (5αR1, 5αR2) is required for normal growth and probably also for development of prostate cancer (PCa). Finasteride, a 5αR2 inhibitor, was shown to reduce the prevalence of PCa in the Prostate Cancer Prevention Trial. However, inhibition of both 5αR isoenzymes causes a greater decrease in serum DHT. The aim of this study was to assess differential expression of these enzymes at various stages of PCa development. METHODS Immunostaining for 5αR1 and 5αR2, using specific, well‐validated antibodies, was evaluated in 26 benign prostatic hyperplasia (BPH) (16 for 5αR2), 53 primary PCa (21 for 5αR2), 18 prostatic intraepithelial neoplasia (PIN), 12 primary PCa treated with neoadjuvant androgen ablation, 15 locally recurrent PCa specimens, and 18 PCa metastases. RESULTS The mean area of moderate plus high intensity staining for 5αR1 increased from 4.8 ± 2.8% of total epithelial area in BPH, to 18.9 ± 5.7% in PIN, 17.0 ± 3.2% in primary cancer, 38.0 ± 7.3% in recurrent cancer, and 55.8 ± 8.5% in PCa metastases. The mean staining area for 5αR2 decreased from 58.8 ± 7.2% in BPH, to 21.1 ± 5.5% in PIN and 34.8 ± 6.7% in primary PCa. Staining for 5αR2 was increased in recurrent cancer and PCa metastases compared to primary PCa, at 58.7 ± 5.2% and 69.2 ± 8.7%, respectively. CONCLUSIONS 5αR1 immunostaining is increased and 5αR2 immunostaining is decreased during development of PCa. In addition, there is increased expression of both 5αR isozymes in recurrent and metastatic cancers, suggesting that both isozymes may be important in the development and progression of PCa. © 2004 Wiley‐Liss, Inc.