title: Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study.
abstract: OBJECTIVE
  Concern about possible false-negative prostate biopsy histopathology findings often leads to rebiopsy. A quantitative methylation specific polymerase chain reaction assay panel, including GSTP1, APC and RASSF1, could increase the sensitivity of detecting cancer over that of pathological review alone, leading to a high negative predictive value and a decrease in unnecessary repeat biopsies.
  
  
  METHODS
  The MATLOC study blindly tested archived prostate biopsy needle core tissue samples of 498 subjects from the United Kingdom and Belgium with histopathologically negative prostate biopsies, followed by positive (cases) or negative (controls) repeat biopsy within 30 months. Clinical performance of the epigenetic marker panel, emphasizing negative predictive value, was assessed and cross-validated. Multivariate logistic regression was used to evaluate all risk factors.
  
  
  RESULTS
  The epigenetic assay performed on the first negative biopsies of this retrospective review cohort resulted in a negative predictive value of 90% (95% CI 87-93). In a multivariate model correcting for patient age, prostate specific antigen, digital rectal examination and first biopsy histopathological characteristics the epigenetic assay was a significant independent predictor of patient outcome (OR 3.17, 95% CI 1.81-5.53).
  
  
  CONCLUSIONS
  A multiplex quantitative methylation specific polymerase chain reaction assay determining the methylation status of GSTP1, APC and RASSF1 was strongly associated with repeat biopsy outcome up to 30 months after initial negative biopsy in men with suspicion of prostate cancer. Adding this epigenetic assay could improve the prostate cancer diagnostic process and decrease unnecessary repeat biopsies.
authors.affiliation: Edinburgh Urological Cancer Group, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Grant D
authors.initials: GD
authors.lastname: Stewart
authors.forename: Leander
authors.initials: L
authors.lastname: Van Neste
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Paul
authors.initials: P
authors.lastname: Delrée
authors.forename: Agnès
authors.initials: A
authors.lastname: Delga
authors.forename: S Alan
authors.initials: SA
authors.lastname: McNeill
authors.forename: Marie
authors.initials: M
authors.lastname: O'Donnell
authors.forename: James
authors.initials: J
authors.lastname: Clark
authors.forename: Wim
authors.initials: W
authors.lastname: Van Criekinge
authors.forename: Joseph
authors.initials: J
authors.lastname: Bigley
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001707:Biopsy, Needle; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm