Finasteride Treatment Has Significant Effect on Androgen Receptor Expression in Prostate Epithelium
Karen A Johnson, William Ricke, Wei Huang. University of Wisconsin, Madison, WI
Background: Finasteride is widely used for the treatment of benign prostatic hyperplasia (BPH). Its therapeutic efficacy is believed to be mediated through selective inhibition of prostatic 5 alpha-reductase (type II), which converts testosterone into more potent dihydrotestosterone (DHT). Limited data is available with regard to finasteride effect on tissue morphology and androgen regulated biomarker expression in BPH tissue.
Design: Transurethral resected prostate (TURP) chips from two groups of patients with BPH were studied: 19 patients treated with finasteride, 25 patients without history of finateride treatment. Prostate tissue H&E sections were reviewed. Tissue sections were also triple-stained with antibodies against prostate specific antigen (PSA), androgen receptor (AR) and basal cell marker (CK5) and visualized with Warp Red, 3,3'-Diaminobenzidine (DAB) and Deep Space Black chromogens respectively. Nuance and inForm software (Perkin Elmer) was used for acquiring images and analysis. The ratio of luminal epithelial cells to basal cells was used to assess the extent of glandular atrophy. Subcellular mean optical density (OD) values of PSA and AR in epithelium and stroma were obtained. IBM SPSS Statistics 19 was used for data analysis.
Results: The AR expression in prostate epithelial nuclei was significantly lower in chips with finateride treatment (mean OD=0.36±0.4) compared to that in chips without finateride treatment (mean OD =0.40±0.05) (p=0.02). The PSA expression in prostate epithelial cytoplasm was also lower in chips with finasteride treatment (mean OD=0.040±0.02) compared to that in chips without finateride treatment (mean OD =0.049±0.03) (p=0.06). No significant difference of stromal nuclear AR levels was observed between these two groups (mean OD=0.11±0.03 vs. mean OD=0.12±0.04, p=0.18). More pronounced glandular atrophic changes and basal cell hyperplasia were observed in TURP chips with finasteride treatment. The ratio of luminal epithelial cells to basal cells was higher in non-finateride treatment group (10.5±17.3) compared to that in finasteride treatment group (6.2±10.0)(p=0.34).
Conclusions: Finasteride treatment has significant effect on prostate epithelial nuclear androgen receptor expression, moderate effect on prostate epithelial PSA expression and morphology and minimal effect on stromal nuclear AR expression.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 150, Wednesday Afternoon