In an attempt to create in microcosm the Selenium and Vitamin E Cancer Trial and to characterize the biologic effects of selenium (SE) and vitamin E (VE) in prostate tissue, 48 presurgical patients with clinically organ-confined prostate cancer were enrolled in a single-institution, randomized, double-blind trial of VE and L-selenomethionine (SeMET) between February 2001 and April 2002 (Kim et al., Proc Am Assoc Cancer Res 2002;43:639). Included were patients scheduled for prostatectomy who had clinical stage T1c/T2 disease, a PSA level <10 ng/mL within 3 months of study registration, and a Gleason score ≤7. Excluded were those taking >50 μg of SeMET and/or ≥300 IU of VE over 3 consecutive days within 1 month of registration. Enrollees received 400 IU of VE, 200 μg of SeMET, a combination of the two, or placebo daily for 3 to 6 weeks. Each also took a multivitamin and 250 mg of vitamin C daily. Diagnostic (pretreatment) biopsy specimens and sections from radical prostatectomy specimens (RPSs) of 36/39 evaluable patients were examined. We derived an apoptotic index (AI) morphologically and a proliferation index (PI) by using immunohistochemistry and counting Ki-67-positive nuclei. Counts were segregated by cell type (normal and cancerous) and by prostate zone (peripheral, transition, and central). The Wilcoxon rank sum test was used to compare AI and PI changes between treatment groups. Multiple linear regression models were fit for AI or PI using nine baseline and posttreatment covariates. Pathologic stages included T2 (32), T3 (3), and T2N1 (1). Total tumor foci in RPSs varied from 1 to 7: 1 (6), 2 (7), 3 (11), 4 (9), 5 (2), and 7 (1). The dominant tumor focus was in the peripheral zone (30), transition zone (5), and central zone (1). Of the 25 patients with matching pre- and posttreatment tumors, 24 had tumors in the peripheral zone, and 1 had tumor in the transition zone. In the comparison of the combination group to the placebo, the AI in normal prostate epithelial cells trended toward a marginally significant increase (p = 0.10). Also, the AI in normal prostate epithelial cells was higher in the transition zone than in the central zone, a difference independent of treatment effects. No trends were observed in the PI between treatment groups in either of the two cell types. SeMET and VE do not seem to affect prostate tissue apoptosis or proliferation significantly; however, the size of the study group and duration of the intervention limit the generalizability of the finding. Although we did not detect morphologic changes induced by SeMET and VE individually or in combination, these may be preceded by modulation of genes mediating the chemopreventive effects of selenium and VE; therefore, a study to assess global gene expression using laser capture microdissection and oligonucleotide microarrays is under way.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]