Scientists at Johns Hopkins have found that measuring the level of a chemical process linked to a genetic change associated with prostate cancer could greatly strengthen standard detection of early-stage curable disease. The report is published in the November 21 issue of the Journal of the National Cancer Institute.
In 1994, Johns Hopkins researchers found that a mutation in a gene that directs the formation of glutathione S-transferase (GSTP1) 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. "Hyper"methylation (too much or abnormal methylation) is a biochemical process that inactivates the GSTP1 gene, shutting off its cancer-preventing properties, and is most often seen in early-stage prostate cancers and rarely in normal or benign prostate disease.
"A genetic marker such as GSTP1 that occurs mostly in early-stage prostate cancers may improve the way we diagnose cancer in the future and help us to catch it early," says David Sidransky, M.D., professor of otolaryngology, oncology and urology and director of the research.
In the current study, Hopkins scientists used a technique called methylation-specific PCR to examine tissue samples from 69 patients with early-stage prostate cancer and 31 patients with benign prostate disease. The researchers also evaluated prostatic intraepithelial neoplasia (PIN) lesions found in 28 of the 69 patients with early-stage disease. PIN lesions are thought to be early precursors of prostate cancer. High levels of GSTP1 methylation were detected in 63 of 69 (91.3 percent) early-stage cancers and in 15 of 28 PIN lesions (53.6 percent). Some GSTP1 methylation was found in nine of 31 samples (29 percent) of benign disease.
To test if GSTP1 methylation could be detected in small biopsy samples, the scientists tested biopsied prostate tissue from 21 patients with high PSA levels. Investigators correctly predicted a diagnosis of prostate cancer in 10 of 11 samples later found to be positive for cancer by pathology. They also correctly excluded a diagnosis of prostate cancer in all 10 patients with no evidence of cancer.
The researchers caution that these are early studies, and additional tests are necessary to verify the usefulness of the diagnostic technique.
Prostate cancer is the second leading cause of cancer death in men in the United States. Approximately 198,100 men were diagnosed last year and an additional 31,500 men died from the disease.
Participants in this study include Henning Usadel from Johns Hopkins; Carmen Jerónimo, Rui Henrique, Jorge Oliveira and Carlos Lopez from Instituto Portugu s de Oncologia de Francisco Genril-Centro Regional do Porto, Portugal; and William Nelson from Johns Hopkins.
Under a license agreement between the Johns Hopkins University and Virco, Ltd., Dr. Sidransky is entitled to a share of royalty received by the University on sales of products embodying the technology reported in this press release. The University and Dr. Sidransky own Virco stock, which is subject to certain restrictions under University policy. Dr. Sidransky is a paid consultant to Virco. The terms of this arrangement are being managed by the University in accordance with its conflict of interest policies.
Jerónimo, Carmen, et al., Quantitation of GSTP1 Methylation in Non-neoplastic Prostatic Tissue and Organ-Confined Prostate Adenocarcinoma. Journal of the National Cancer Institute, 2001, vol. 93, no. 22.
Related Web site:
Johns Hopkins Oncology Center: http://www.hopkinscancercenter.org
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Journal
JNCI Journal of the National Cancer Institute