Epigenetic Field Effects: Potential Applications For Detection Of Occult High-Grade Prostate Cancer

20 Background: Needle biopsy (Bx) pathology is central to the diagnosis and management of prostate cancer (PCa), but Bx sampling error can result in an underestimate of Gleason grade (GS). Epigenetic DNA hypermethylation markers associated with PCa are commonly observed in histologically benign tissue adjacent to a cancer focus. Such field effects are the basis for a diagnostic test in which the absence of GSTP1, APC and RASSF1 hypermethylation in benign Bxs is associated with a low risk of “missed” PCa. Relatively low methylation thresholds are used for the current epigenetic test (ConfirmMDx) that is designed to be sensitive to any occult cancer, regardless of GS. We are evaluating new prototype epigenetic tests that are designed to be sensitive to the GS of an occult PCa. Methods: DNA was extracted from prostate bx tissue prints and used for quantitative methylation-specific PCR for GSTP1, APC and RASSF1. Results were computed as levels of marker methylation relative to a common reference gene. Each of...