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Background: Hypermethylation of the CpG island at the promoter region of the π-class glutathione S-transferase gene (GSTP1) is the most common somatic genome abnormality in human prostate cancer. We evaluated GSTP1 CpG island hypermethylation as a prognostic biomarker in the serum of men with prostate cancer. Methods: GSTP1 CpG island hypermethylation was detected using a restriction endonuclease quantitative PCR technique. We analyzed preoperative serum from 85 men with clinically localized prostate cancer treated with radical prostatectomy and from 35 men with a negative prostate biopsy. We then assayed preoperative serum from a dataset of 55 pairs of men with clinically localized prostate cancer treated with radical prostatectomy, matched for Gleason score, comprising 55 men suffering PSA recurrence (median 2 years) and 55 men who were free of disease at last follow-up (median 3 years). The association of serum GSTP1 CpG island hypermethylation and PSA recurrence was determined. Results: GSTP1 CpG island hypermethylation was not detected in the serum of men with a negative prostate biopsy, but was detected in 12% of men with clinically localized disease and 28% of men with metastatic cancer (p=0.003). In the matched dataset, eight men (15%) who developed PSA recurrence were positive for GSTP1 CpG hypermethylation, while no patient who was free of disease was positive for GSTP1 CpG island hypermethylation (McNemar test,chi square=6.1,p=0.01). In a multivariable analysis that accounted for recognized prognostic factors, positive GTSP1 CpG island hypermethylation was the most significant predictor of PSA recurrence (HR 4.4 [95% CI (2.2, 8.8)],p<0.001). Conclusion: Our study suggests that GSTP1 CpG island hypermethylation may be an important DNA-based prognostic serum biomarker for prostate cancer.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]