The Usefulness of the Detection of GSTP1 Methylation in Urine as a Biomarker in the Diagnosis of Prostate Cancer

Abstract

Prostate cancer has a unique set of problems associated with its early detection and diagnosis that might be aided by the addition of molecular markers, such as DNA hypermethylation. DNA methylation is an important epigenetic mechanism of gene regulation that has a critical role in normal developmental processes. Aberrant DNA methylation is a hallmark of carcinogenesis and GSTP1 hypermethylation is the most common molecular alteration in human prostate cancer. To our knowledge the clinical usefulness of the detection of gene methylation is yet to be established. We evaluated GSTP1 hypermethylation in urine collected after prostatic massage and in core needle biopsies from 100 men referred for diagnostic biopsy. Methylation of GSTP1 in urine specimens had 75% sensitivity and 98% specificity for prostate cancer. GSTP1 methylation in the biopsy had 88% specificity and 91% sensitivity. Interestingly we observed a higher frequency of GSTP1 methylation in the urine of men with stage III vs II disease (100% vs 20%, p = 0.05). This study suggests that the detection of GSTP1 methylation in prediagnostic urine may improve the specificity of PSA and help distinguish men with prostate cancer from those with benign prostatic hyperplasia. This finding should be further explored in a larger, prospective screening trial.