Prostate cancer detection by GSTP1 methylation analysis of postbiopsy urine specimens.
OBJECTIVE
We assess the feasibility of a urinary test for prostate cancer detection in a high-risk patient cohort based on methylation-specific PCR analysis of the pi class glutathione S-transferase (GSTP1) gene promoter.


METHODS
A total of 45 men underwent transrectal ultrasound-guided biopsy of the prostate for suspected malignancy. Clean-catch voided urine specimens were prospectively collected from each patient immediately after biopsy. Genomic DNA was isolated from urine specimens and subjected to sodium bisulfite modification. Methylation of the GSTP1 promoter was examined in a blinded manner by methylation-specific PCR analysis and correlated with pathology results, and clinical information was obtained from the patient record.


RESULTS
Methylation of GSTP1 in the urine was detected in a total of 18 of 36 (50%) informative cases. A total of 7 of 18 (39%) patients with prostate adenocarcinoma identified on their initial biopsy had detectable urinary GSTP1 methylation (58% sensitivity among informative cases). Abnormal urinary GSTP1 methylation was also detected in 7 of 21 (33%) patients without evidence of cancer on biopsy and in 4 of 6 (67%) patients diagnosed with atypia or high-grade prostatic intraepithelial neoplasia.


CONCLUSIONS
We have demonstrated the feasibility of a novel, noninvasive molecular approach for the detection of epigenetic changes associated with prostate cancer. A screening test based on GSTP1 methylation in the urine specimens of patients with suspected prostate malignancy may be a useful adjunct to serum screening tests and digital rectal examination findings for identification of men at increased risk of harboring cancer despite a negative biopsy. This molecular assay has potential application for stratification of patients into low- and high-risk groups for surveillance versus repeat biopsy.
Gonzalgo
Mark L
ML
The James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2101, USA.
Pavlovich
Christian P
CP
Lee
Shing M
SM
Nelson
William G
WG
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015331:Cohort Studies; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism* / Q000652:urine*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism* / Q000652:urine*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019048:Prostatic Intraepithelial Neoplasia / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D012680:Sensitivity and Specificity; D013447:Sulfites / Q000378:metabolism / Q000494:pharmacology
D007527:Isoenzymes; D013447:Sulfites; D004247:DNA; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C009279:sodium bisulfite