Epigenetic Field Effect Markers As Indicative Of Occult High-Grade Prostate Cancer

116 Background: Epigenetic changes through DNA methylation can serve as biomarkers for the presence of prostate cancer (PCa). Gene methylation in histologically benign tissue adjacent to PCa can provide "field effect" biomarkers to detect cancer missed due to sampling errors. Such errors may also result in underestimates of PCa stage or grade, complicating decisions about Active Surveillance. We previously showed increased field effect methylation in GS 7 over GS 6 subjects in a small patient cohort. Here, established methylation markers of PCa (GSTP1, APC and RASSF1) were tested in a larger cohort to compare histologically benign biopsy cores from patients diagnosed with no cancer, low volume GS 6 cancer and GS 7 cancer. The objective was to confirm that epigenetic field effects may be useful for detecting occult high grade malignancies in diagnostic and prognostic settings.DNA was extracted from prostate biopsy tissue prints and used for multiplex methylation-specific PCR (MSP) assays of the 3 genes. All testing was done blinded. Each of 12 tissue cores was tested from a series of 76 biopsy patients: 34 diagnosed with GS 6 PCa, 22 with GS 7 PCa, and 20 no-cancer controls.In 19 of the 22 GS 7 cases (86%), epigenetic markers were positive for field effects in one or more adjacent benign cores; 12 (54%) were positive for all 3 epigenetic markers. In contrast, only 9 of 34 cases (26%) GS 6 cases were positive for all 3 markers. We again observed that robust marker expression in histologically benign cores from cases diagnosed with low volume GS 6 PCa was associated with higher grade cancer at radical prostatectomy (upgrading). APC showed the best performance as a single marker "field effect" test for adjacent high grade PCa.GSTP1, APC and/or RASSF1 gene promoter methylation was observed to be more prevalent in histologically benign cores from biopsy patients diagnosed with GS 7 PCa, as compared with low volume GS 6. This study confirms previous findings in a larger cohort of subjects that these "field effect" biomarkers can be useful for detecting cancer adjacent to histologically negative biopsies and may be indicative of occult aggressive PCa.