Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate cancer (PCa)

Seeking insight into the possible role of estrogens in prostate cancer (PCa) evolution, we assayed serum E-2, estrone (E-1), and estrone sulfate (El S) in 349 PCa and 100 benign prostatic hyperplasia (BPH) patients, and in 208 control subjects in the same age range (50-74 years). E-1 (pmoI/L +/- S.D.) and E, S (nmol/L +/- S.D.) in the PCa and BPH patients (respectively 126.1 +/- 66.1 and 2.82 +/- 1.78, and 127.8 +/- 56.4 and 2.78 +/- 2.12) were significantly higher than in the controls (113.8 +/- 47.6 and 2.11 +/- 0.96). E-2 was not significantly different among the PCa, BPH, and control groups. These assays were also carried out in PCa patients after partition by prognosis (PSA, Gleason score (GS), histological stage, and surgical margins (SM)). Significantly higher E, S levels were found in PCa with: PSA > 10 ng/L (3.05 +/- 1.92) versus PSA <= 10 ng/mL (2.60 +/- 1.55), stage pT3-T4 (2.99 +/- 1.80) versus pT2 (2.58 +/- 1.58), and positive (3.26 +/- 1.95) versus negative margins (2.52 +/- 1.48). E-1 was higher in poor- than in better-prognosis PCa. E-2 was significantly higher in PCa with GS >= 4 + 3 (109.5 +/- 43.8) versus GS <= 3 + 4 (100.6 +/- 36.5) and increased significantly when GS increased from 3+3 to 4+4. Estrogens, especially E1S appeared to be possible markers of PCa progression. Attempting to identify potential sources of E-2 in PCa according to prognosis, as well as in BPH, we found a significant correlation coefficient between EIS and E2 (0.266-0.347) in poor-prognosis PCa and no correlation in BPH (0.026) and better-prognosis PCa (0.013-0.104). It is as though during progression of PCa from good to poor prognosis there were a shift in the E-1 to E-2 metabolic pathway from predominantly oxidative to predominantly reductive. (C) 2008 Elsevier Ltd. All rights reserved.