Levels of 5alpha-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer.

Abstract

In the prostate testosterone is converted to dihydrotestosterone by 5alpha-reductase type 1 and/or 2. Although 5alpha-reductase type 2 is predominant in normal prostates, type 1 is increased in cancer vs benign tissue. It is unclear whether 5alpha-reductase type 1/2 levels correlate with cancer grade. We compared the relative expression of 5alpha-reductase type 1 and 2 in localized high and low grade prostate cancer. Immunostaining for 5alpha-reductase type 1/2 was evaluated in 64 prostate tissues from untreated men with localized prostate cancer. The percent of tumor area with moderate-high intensity staining was estimated for each Gleason pattern in the tissues. Adjacent benign tissue was evaluated in 26 prostate cancer specimens. Moderate-high staining for 5alpha-reductase type 1 increased from 18.8% +/- 2.9% (mean +/- SEM) in 34 Gleason pattern 3 cancers to 31.0% +/- 4.1% in 30 Gleason pattern 4/5 cancers (p = 0.016). Staining for 5alpha-reductase type 2 increased from 22.9% +/- 3.0% in 34 Gleason pattern 3 cancers to 39.2% +/- 4.1% in 30 Gleason pattern 4/5 cancers (p = 0.002). Compared to benign prostatic hyperplasia tissues staining for 5alpha-reductase type 1 was greater than 3-fold higher and staining for 5alpha-reductase type 2 was significantly lower in benign tissue adjacent to cancer (p = 0.006 and 0.0236, respectively). Levels of 5alpha-reductase type 1 and 2 are increased in localized high vs low grade prostate cancer. Levels of 5alpha-reductase type 1 are higher in benign tissue adjacent to cancer than in benign prostatic hyperplasia. These results raise the possibility that increased 5alpha-reductase type 1 in localized high grade cancers may contribute to the decreased effectiveness of the 5alpha-reductase type 2 selective inhibitor finasteride against high grade prostate cancer in the Prostate Cancer Prevention Trial.