title: Fluorescent methylation-specific polymerase chain reaction for DNA-based detection of prostate cancer in bodily fluids.
abstract: Promoter hypermethylation of the glutathione S-transferase P1 gene (GSTP1) is the most frequent DNA alteration in prostatic carcinoma. Because this epigenetic DNA alteration can be reliably detected by methylation-specific PCR (MSP), we applied this new technique for molecular detection of prostate cancer in various human bodily fluids. We investigated GSTP1 promoter hypermethylation in DNA isolated from plasma, serum, ejaculate, and urine after prostate massage and from prostate carcinoma tissues from 33 patients with prostate cancer and 26 control patients with benign prostatic hyperplasia (BPH). Fluorescently labeled MSP products were analyzed on an automated gene sequencer. Whereas GSTP1 promoter hypermethylation was not detectable by MSP in prostate tissue and bodily fluids from patients with BPH, we found it in 94% of tumors (16 of 17), 72% of plasma or serum samples (23 of 32), 50% of ejaculate (4 of 8) and 36% of urine (4 of 11) from patients with prostate cancer. Additionally, MSP identified circulating tumor cells in 30% (10 of 33) of prostate cancer patients. Analysis of GSTP1 promoter hypermethylation by MSP thus provides a specific tool for molecular diagnosis of prostate cancer in bodily fluids.
authors.affiliation: Department of Urology, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany. goessl@zedat.fu-berlin.de
authors.forename: C
authors.initials: C
authors.lastname: Goessl
authors.forename: H
authors.initials: H
authors.lastname: Krause
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Heicappell
authors.forename: M
authors.initials: M
authors.lastname: Schrader
authors.forename: J
authors.initials: J
authors.lastname: Sachsinger
authors.forename: K
authors.initials: K
authors.lastname: Miller
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000368:Aged; D001826:Body Fluids / Q000737:chemistry; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D005456:Fluorescent Dyes; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012661:Semen / Q000737:chemistry
chemical_list: D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase