Novel approaches for the early detection and management of
prostate cancer are urgently needed. Clonal genetic alterations have been used as targets for the detection of neoplastic cells in bodily fluids from many
cancer types. A similar strategy for molecular diagnosis of
prostate cancer requires a common and/or early genetic alteration as a specific target for neoplastic prostate cells. Hypermethylation of regulatory sequences at the
glutathione S-transferase pi (GSTP1) gene locus is found in the majority (>90%) of primary prostate
carcinomas, but not in normal prostatic tissue or other normal tissues. We hypothesized that urine from
prostate cancer patients might contain shed neoplastic cells or debris amenable to
DNA analysis. Matched specimens of primary
tumor, peripheral blood lymphocytes (normal control), and simple voided urine were collected from 28 patients with
prostate cancer of a clinical stage amenable to cure. Genomic
DNA was isolated from the samples, and the methylation status of GSTP1 was examined in a blinded manner using methylation-specific PCR. Decoding of the results revealed that 22 of 28 (79%) prostate
tumors were positive for GSTP1 methylation. In 6 of 22 (27%) cases, the corresponding urine-sediment
DNA was positive for GSTP1 methylation, indicating the presence of neoplastic
DNA in the urine. Furthermore, there was no case where urine-sediment
DNA harbored methylation when the corresponding
tumor was negative. Although we only detected GSTP1 methylation in under one-third of voided urine samples, we have demonstrated that molecular diagnosis of prostate
neoplasia in urine is feasible. Larger studies focusing on
carcinoma size, location in the prostate, and urine collection techniques, as well as more sensitive technology, may lead to the useful application of GSTP1 hypermethylation in
prostate cancer diagnosis and management.