title: Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage.
abstract: OBJECTIVE
  The diagnosis of localized prostate cancer is difficult due to a lack of cancer-specific biomarkers. Many patients require repeat prostate biopsies to diagnose the disease. We investigated whether aberrant promoter hypermethylation in prostatic fluid could reliably detect prostate cancer.
  
  
  METHODS
  Urine samples were collected after prostate massage from 95 patients with localized prostate cancer undergoing radical prostatectomy (63 pT(1), 31 pT(2), and 1 pT(3)) and from 38 control patients. Ten genes (GSTP1, RASSF1a, ECDH1, APC, DAPK, MGMT, p14, p16, RARbeta2, and TIMP3) were investigated using quantitative real-time methylation-specific PCR. Receiver operator curves were generated.
  
  
  RESULTS
  The frequency of gene methylation ranged from 6.3% (p14) to 83.2% (GSTP1) in prostate cancer patients. At least one gene was hypermethylated in 93% of cancer patients. The specificity of methylation was 0.74. Methylation was significantly more frequent (P < 0.05) in cancer than control patients for all genes except p14 and p16. According to receiver operator curve analysis, the four-gene combination of GSTP1 (0.86), RASSF1a (0.85), RARbeta2 (0.80), and APC (0.74) best discriminated malignant from nonmalignant cases. The sensitivity and accuracy of this four-gene set were 86% and 89%, respectively.
  
  
  CONCLUSIONS
  The presence of aberrant methylation in urinary cells obtained after prostate massage is significantly associated with prostate cancer. A panel of four genes could stratify patients into low and high risk of having prostate cancer and optimize the need for repeat prostatic biopsies.
authors.affiliation: Institute for Cancer Studies and Academic Urology Unit, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK. mroupret@club-internet.fr
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.forename: Vincent
authors.initials: V
authors.lastname: Hupertan
authors.forename: David R
authors.initials: DR
authors.lastname: Yates
authors.forename: James W F
authors.initials: JW
authors.lastname: Catto
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Rehman
authors.forename: Mark
authors.initials: M
authors.lastname: Meuth
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ricci
authors.forename: Roger
authors.initials: R
authors.lastname: Lacave
authors.forename: Géraldine
authors.initials: G
authors.lastname: Cancel-Tassin
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.forename: François
authors.initials: F
authors.lastname: Rozet
authors.forename: Xavier
authors.initials: X
authors.lastname: Cathelineau
authors.forename: Guy
authors.initials: G
authors.lastname: Vallancien
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000652:urine; D004247:DNA / Q000032:analysis / Q000302:isolation & purification / Q000652:urine; D019175:DNA Methylation; D006801:Humans; D008297:Male; D008405:Massage; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D012680:Sensitivity and Specificity; D014556:Urine / Q000166:cytology*
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA