Quantitative GSTP1 hypermethylation in bodily fluids of patients with prostate cancer.
OBJECTIVE
To further determine the value of real-time quantitative methylation-specific polymerase chain reaction (MSP) of GSTP1 as a molecular tool for the detection of prostate adenocarcinoma. Recent studies have shown a high frequency (more than 90%) of GSTP1 gene promotor methylation in prostate adenocarcinoma and a lower frequency in DNA from serum and urine.


METHODS
Tissue samples from 69 patients with early-stage prostate adenocarcinoma and 31 patients with benign prostatic hyperplasia were collected. Matched urine and plasma specimens were obtained preoperatively. After sodium-bisulfite treatment, extracted DNA was analyzed for GSTP1 promoter hypermethylation both by conventional and real-time quantitative MSP.


RESULTS
In tissue samples, GSTP1 hypermethylation was detected in 63 (91.3%) of the 69 patients with cancer and in 9 (29%) of the 31 patients with benign prostatic hyperplasia. Conventional MSP detected GSTP1 hypermethylation in a larger number of urine and plasma samples than did real-time quantitative MSP (53.6% versus 31.9%, overall). In all positive bodily fluids, the paired tumor was also confirmed to be methylated. GSTP1 hypermethylation was detected by both MSP methods in only one urine sample (3.2%) from a patient with benign prostatic hyperplasia.


CONCLUSIONS
Although not quantitative, conventional MSP is currently more sensitive than real-time quantitative MSP in the detection of GSTP1 hypermethylation in bodily fluids from patients with prostate cancer with clinically localized disease. The value of quantitative determinations in monitoring and risk assessment remains to be further explored.
Jerónimo
Carmen
C
Department of Otolaryngology, Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Usadel
Henning
H
Henrique
Rui
R
Silva
Cristina
C
Oliveira
Jorge
J
Lopes
Carlos
C
Sidransky
David
D
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D003937:Diagnosis, Differential; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D011470:Prostatic Hyperplasia / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000652:urine
D004273:DNA, Neoplasm; D007527:Isoenzymes; D009363:Neoplasm Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase