High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients.
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.
Henrique
Rui
R
Department of Pathology, Portuguese Oncology Institute--Porto, Portugal.
Ribeiro
Franclim R
FR
Fonseca
Daniel
D
Hoque
Mohammad O
MO
Carvalho
André L
AL
Costa
Vera L
VL
Pinto
Mafalda
M
Oliveira
Jorge
J
Teixeira
Manuel R
MR
Sidransky
David
D
Jerónimo
Carmen
C
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
D025601:Adenomatous Polyposis Coli Protein