High concordance of gene methylation in post-digital rectal examination and post-biopsy urine samples for prostate cancer detection.
OBJECTIVE
We evaluated the concordance between post-digital rectal examination and post-prostate biopsy urine samples using conventional methylation specific polymerase chain reaction analysis of 3 gene promoters in patients with suspected or confirmed prostate cancer.


METHODS
Voided urine specimens were collected from 17 men after 15-second digital rectal examination and again after transrectal ultrasound guided biopsy of the prostate for suspected malignancy or for followup 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 was determined by conventional methylation specific polymerase chain reaction analysis in post-digital rectal examination and post-biopsy samples, and correlated with clinical information.


RESULTS
Prostate cancer was detected on prostate biopsy in 12 of 17 patients (71%). Promoter methylation was detected in post-digital rectal examination urine specimens for GSTP1 (24%), APC (12%) and EDNRB (66%). Promoter methylation was detected in post-biopsy urine specimens for GSTP1 (18%), APC (18%) and EDNRB (77%). The concordance between post-digital rectal examination and post-biopsy urine samples was 94% for GSTP1 and APC, and 82% for EDNRB. Overall 100% of patients with biopsy proven prostate cancer had at least 1 gene methylated in urine vs 60% of those without evidence of prostate cancer on biopsy.


CONCLUSIONS
Gene analysis using conventional methylation specific polymerase chain reaction is a reliable method for detecting abnormal DNA methylation in voided urine samples obtained following digital rectal examination or prostate needle biopsy. The concordance between post-digital rectal examination and post-biopsy urinary samples for promoter methylation is high (82% to 94%), suggesting that urine collected after digital rectal examination may be used for genetic analysis with results similar to those in post-biopsy urine samples.
Rogers
Craig G
CG
The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. crogers6@jhmi.edu
Gonzalgo
Mark L
ML
Yan
Gai
G
Bastian
Patrick J
PJ
Chan
David Y
DY
Nelson
William G
WG
Pavlovich
Christian P
CP
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D001706:Biopsy; D019175:DNA Methylation; D051517:Digital Rectal Examination; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D044023:Receptor, Endothelin B / Q000235:genetics*
D025601:Adenomatous Polyposis Coli Protein; D044023:Receptor, Endothelin B; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi