Leonel Maldonado1, Mariana Brait2, Myriam Loyo2, Lauren Sullenberger2, Kevin Wang2, Sarah B Peskoe3, Eli Rosenbaum2, Roslyn Howard2, Antoun Toubaji4, Roula Albadine4, George J Netto5, Mohammad O Hoque2, Elizabeth A Platz6, David Sidransky7. 1. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 4. Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 5. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 6. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 7. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. Electronic address: dsidrans@jhmi.edu.
Abstract
PURPOSE: Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors. MATERIALS AND METHODS: We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p ≤0.05 considered statistically significant. RESULTS: The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05). CONCLUSIONS: Greater GSTP1 promoter methylation in cancer tissue was independently associated with the risk of recurrence in patients with early prostate cancer. This suggests that GSTP1 promoter methylation may be a potential tissue based recurrence marker.
PURPOSE: Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors. MATERIALS AND METHODS: We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p ≤0.05 considered statistically significant. RESULTS: The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05). CONCLUSIONS: Greater GSTP1 promoter methylation in cancer tissue was independently associated with the risk of recurrence in patients with early prostate cancer. This suggests that GSTP1 promoter methylation may be a potential tissue based recurrence marker.
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