Hypermethylation an Indicator of Prostate Cancer

The study, conducted by researchers at Johns Hopkins University School of Medicine (Baltimore, MD, USA), was published in the November 21, 2001, issue of the Journal of the National Cancer Institute.

In earlier studies, the researchers had found that a mutation in a gene that directs the formation of glutathione-S (GST-Pi) alters levels of an enzyme that detoxifies environmental carcinogens and protects against cancer. Changes in this gene lead to hypermethylation, now known to be the most common genetic error in prostate cancer, according to the researchers. In the current study, they used methylation-specific PCR to examine tissue samples from 69 patients with early-stage prostate cancer and 31 patients with benign prostatic disease. High levels of GST-Pi methylation were detected in 63 of the 69 patients with early-stage disease.

The researchers also evaluated prostatic intraepithelial neoplasia (PIN) lesions found in 28 of 69 patients with early-stage disease. PIN lesions are thought to be early precursors of prostate cancer. High levels of GST-PI were found in 15 of the 28. To learn if GST-Pi could be detected in small biopsy samples, the researchers tested biopsied prostate tissue from 21 patients with high prostate-specific antigen (PSA) levels. They were able to correctly predict a diagnosis of prostate cancer in 10 of 11 samples found to be positive for cancer by pathologic review. They also correctly excluded a diagnosis of prostate cancer in all 10 of patients without cancer.

"We are very pleased with the results of these findings, and further testing will determine if GST-Pi measurement can help diagnose patients early enough to provide curative therapy,” said Dr. Herman Spolders, president of OncoGenome Sciences (Mechelen, Belgium), which is developing a commercial diagnostic assay based on the research.




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