title: High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients.
abstract: OBJECTIVE
  Prostate cancer is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. Owing to the limitations of current clinical, serologic, and pathologic parameters in predicting disease progression, we sought to investigate the prognostic value of promoter methylation of a small panel of genes by quantitative methylation-specific PCR (QMSP) in prostate biopsies.
  
  
  METHODS
  Promoter methylation levels of APC, CCND2, GSTP1, RARB2, and RASSF1A were determined by QMSP in a prospective series of 83 prostate cancer patients submitted to sextant biopsy. Clinicopathologic data [age, serum prostate-specific antigen (PSA), stage, and Gleason score] and time to progression and/or death from prostate cancer were correlated with methylation findings. Log-rank test and Cox regression model were used to identify which epigenetic markers were independent predictors of prognosis.
  
  
  RESULTS
  At a median follow-up time of 45 months, 15 (18%) patients died from prostate cancer, and 37 (45%) patients had recurrent disease. In univariate analysis, stage and hypermethylation of APC were significantly associated with worse disease-specific survival, whereas stage, Gleason score, high diagnostic serum PSA levels, and hypermethylation of APC, GSTP1, and RASSF1A were significantly associated with poor disease-free survival. However, in the final multivariate analysis, only clinical stage and high methylation of APC were significantly and independently associated with unfavorable prognosis, i.e., decreased disease-free and disease-specific survival.
  
  
  CONCLUSIONS
  High-level APC promoter methylation is an independent predictor of poor prognosis in prostate biopsy samples and might provide relevant prognostic information for patient management.
authors.affiliation: Department of Pathology, Portuguese Oncology Institute--Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Franclim R
authors.initials: FR
authors.lastname: Ribeiro
authors.forename: Daniel
authors.initials: D
authors.lastname: Fonseca
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Hoque
authors.forename: André L
authors.initials: AL
authors.lastname: Carvalho
authors.forename: Vera L
authors.initials: VL
authors.lastname: Costa
authors.forename: Mafalda
authors.initials: M
authors.lastname: Pinto
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D019175:DNA Methylation; D018450:Disease Progression; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D025601:Adenomatous Polyposis Coli Protein