GSTP1 Methylation Level/Malignant V Benign Disease

GSTP1 Methylation Level Discriminates Malignant From Benign Prostate Disease

November 21, 2001WESTPORT (Reuters Health)

The quantitation of GSTP1 methylation in prostate tissue samples accurately discriminates between normal hyperplastic tissue and prostatic carcinoma, according to a report in the November 21st Journal of the National Cancer Institute.

"PSA screening has helped diagnose many men with prostate cancer and has saved countless lives, but it is far from perfect," Dr. David Sidransky from The Johns Hopkins University School of Medicine in Baltimore commented to Reuters Health. "A molecular test that can correctly identify those with cancer and exclude those with benign disease could help triage these patients early on in their evaluation for observation or treatment."

Dr. Sidransky and colleagues used a highly sensitive and reproducible PCR method to measure GSTP1 methylation in prostate tissue samples from 31 men with benign prostatic hyperplasia (BPH) and from 69 men with early-stage prostatic adenocarcinoma, some of whom also had prostatic intraepithelial neoplasia.

The GSTP1 to MYOD1 (a reference gene) methylation ratios differed significantly among the three types of tissues, with medians of 0.0 for BPH, 1.4 for prostatic intraepithelial neoplasia, and 250.8 for prostate adenocarcinoma, the researchers report.

Using a cutoff level of 10.0 for GSTP1/MYOD1 methylation ratios, the sensitivity of the test in detecting prostate adenocarcinoma was 85.5% and the positive predictive value was 100%, the report indicates.

"This study demonstrates that quantitation of GSTP1 methylation may be a useful marker for prostate cancer in patients with clinically localized disease," the authors conclude. "Because so many patients at risk for prostate cancer present with a high serum PSA, quantitation of GSTP1 methylation in tissue biopsy specimens could augment current diagnostic histology and facilitate the triage of patients into appropriate risk categories for further intervention."

"Prospective trials are underway to better understand the value of the test in the above settings," Dr. Sidransky said. "Our expectation is that the sensitive molecular readout will help in cases where the definitive diagnosis of cancer cannot be established from the biopsy slides."

J Natl Cancer Inst 2001;93:1747-1752.

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