Epidemiologic studies have shown lower incidence of prostate cancer in patients with high dietary intake of lycopene. Here, we present preliminary data from a Phase 2 trial involving patients with biopsy-confirmed HGPIN. Following a baseline 12-core biopsy that is negative for cancer (but positive for HGPIN), participants were randomly assigned to placebo or 2 daily LycoMato® capsules (total = 30 mg lycopene) for a period of 6 months, and then re-biopsied. In this analysis, we evaluated the pre- and post- treatment total epithelial area, and the area of HGPIN lesions in prostatic biopsies. 38 patients have consented to participate thus far, 23 of whom have completed the trial. We present data from a random sample of 10 of these 23 patients; 7 of whom received LycoMato while the other 3 received placebo. Two 5μ sections were cut from the pre- and post-treatment biopsy blocks of these participants, one for H&E staining and the other for immunostaining with a mouse monoclonal, pancytokeratin (PanCk) antibody and DAB as the chromagen. The immunostained slides were digitally scanned at 20x using an Aperio ScanScope®. The amount of PanCk area (total brown pixels) was computed using the Positive Pixel Algorithm and expressed as a percentage of the total tissue area. Area of HGPIN lesions were computed by drawing regions of interests (ROI). In the placebo group, the mean epithelial area percentage pre- and post-treatment was 14.6% and 10.0% respectively; among treated subjects, these areas were 21.6% and 17.8%. Thus, no significant change in epithelial area was observed (P = 0.89). Due to re-sectioning of the paraffin blocks, HGPIN was identified in 4 pre-treatment biopsies from the lycopene group and was found again post-treatment on 2 of these. Only one subject from the placebo group had identifiable HGPIN pre-treatment, and this was absent post-treatment. In the lycopene group, the mean percentage of epithelial area occupied by HGPIN pre-and post-treatment was 1.21% and 0.76%, respectively. These results are too sparse to interpret; however, biopsies from additional subjects completing the trial are currently being analyzed. Because of spatial sampling errors, use of HGPIN status or percent area as endpoints will require larger study sizes to detect small-moderate effects. Targeting of biomarkers in histologically normal tissue will provide a more efficient way of studying endpoints in this trial.

[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]