High Promoter Methylation Levels of APC Predict Poor Prognosis in Sextant Biopsies from Prostate Cancer Patients
Purpose: 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 pr...
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Veröffentlicht in: | Clinical cancer research 2007-10, Vol.13 (20), p.6122-6129 |
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Sprache: | eng |
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Zusammenfassung: | Purpose: 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.
Experimental Design: 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. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-07-1042 |