Association of ERG-PTEN expression profile of prostate biopsy with PSA velocity.

Abstract

92 Background: Although ERG and PTEN expression has demonstrated to have a role in prostate carcinogenesis, its association with important clinical markers such as PSA velocity (rate of prostate specific antigen [PSA] change over time) is currently unknown. This novel pilot study presents the results of the above association with the aim of understanding its clinical utility. Methods: Data for this study was obtained from men enrolled in a phase 2 clinical trial conducted to determine the effect of selenium supplementation on prostate cancer progression. All men in this trial were diagnosed with prostate cancer and opted for watchful waiting as their treatment modality. Biopsy tissue collected at randomization was stained for ERG and PTEN using immunohistochemistry techniques. PSA was measured at baseline and at each follow-up visit (every three months). PSA velocity was calculated using mixed effects regression models and the study group was divided into three tertiles. Results: Data from 77 subjects indicates ERG and PTEN expression is independently associated with lower PSA velocity (p = 0.02 and 0.037 respectively). Joint effect of ERG and PTEN expression on PSA velocity was also analyzed using logistic regression. As compared to the wild type (ERG+/PTEN-), ERG-/PTEN- and ERG-/PTEN+ subjects demonstrated increased risk for high PSA velocity. Odds ratios (95% confidence intervals) are: 4.05 (0.68, 24.1) and 1.71 (0.12, 23.1), respectively. These models were adjusted for age, race and Gleason score. Conclusions: This is the first study to report on an association between ERG-PTEN expression and PSA velocity, an important clinical marker of aggressive prostate cancer. Results of this study are counterintuitive to the current understanding of ERG-PTEN mechanism in prostate carcinogenesis indicating presence of yet undiscovered molecular pathways. Hence further research is needed to delineate these pathways and determine clinical utility of ERG and PTEN expression in prostate cancer.