High Concordance Between Post-DRE and Post-Biopsy Urine Samples for Gene Methylation using MSP Analysis

Craig G Rogers, Gai Yan, Mark L Gonzalgo, David Chan, William G Nelson, Christian P Pavlovich
Johns Hopkins University School of Medicine, Baltimore, MD

Introduction:
To evaluate the concordance between post-digital rectal exam (DRE) and post-prostate biopsy urine samples using conventional methylation-specific PCR (MSP) analysis of three different gene promoters in patients with suspected or confirmed prostate cancer (PCA).
Methods:
Voided urine specimens were collected from 17 men after DRE and again after transrectal ultrasound-guided biopsy of the prostate for suspected malignancy or for follow-up biopsy as part of an expectant management protocol. Urine sediment DNA was isolated and subjected to bisulfite modification. Methylation of GSTP1, EDNRB, and APC promoters were determined by conventional MSP analysis for both post-DRE and post-biopsy samples and correlated with clinical information.
Results:
PCA was detected on prostate biopsy in 12 of 17 (71%) patients. Promoter methylation was detected in post-DRE urine specimens for GSTP1 (29%), EDNRB (58%), and APC (12%). Promoter methylation was detected in post-biopsy urine specimens for GSTP1 (24%), EDNRB (83%), and APC (18%). The concordance between post-DRE and post-biopsy urine samples was 94% (GSTP1 and APC) and 84% (EDNRB). Overall, 100% of patients with PCA had at least one gene methylated in the urine vs. 58% of patients without PCA.
Conclusions:
Gene analysis using conventional MSP is a reliable method for detecting abnormal DNA methylation in voided urine samples obtained following DRE or prostate needle biopsy. The concordance between post-DRE and post-biopsy urinary samples for promoter methylation is high (84-94%), suggesting that that urine collected after DRE may be used for genetic analysis with similar results to post-biopsy urine samples.

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