ANN ARBOR, MI -- Oct. 9, 2002 -- High levels of activity in a specific gene could be a warning that prostate cancer is about to begin spreading throughout the body, according to a new study.
A team of scientists led by Dr. Arul Chinnaiyan at the University of Michigan's Comprehensive Cancer Center showed that the gene called EZH2 was at "the top of the list" of 55 genes found to be more active in prostate cancer that had spread or metastasized than in localized prostate cancer. The researchers published their findings in an article in the Oct. 10 issue of Nature.
"We found the greatest EZH2 overexpression in metastatic prostate cancer tissue," Chinnaiyan said in a prepared statement. "At this point, it's unclear whether the gene plays a role in cancer's development or is simply an indicator of lethal progression."
The research team used advanced DNA microarray technology to observe the activity level of dozens of genes involved in solid tumors that had begun spreading beyond the initial tumor site.
After identifying EZH2 as highly active, the researchers analyzed 278 tissue samples from 64 men for EZH2 protein expression, as well as other common prognostic indicators used by pathologists, such as Gleason score, tumor stage or PSA levels. They found EZH2 protein expression to be significantly better at predicting clinical outcome than any other factor.
To validate their DNA microarray results, the researchers analyzed levels of EZH2 protein in more than 1,000 prostate tissue samples. They included normal prostate tissue, tissue with non-malignant cell changes, and tissue with localized and advanced cancer.
When they compared the prostate tissue samples, the quantity of EZH2 protein increased steadily as the samples progressed from benign to clinically localized prostate cancer to metastatic disease. The highest EZH2 concentrations were found in metastatic prostate cancer.
EZH2 is one of several related proteins that control a cell's genetic memory and interfere with transcription – the process cells use to transcribe or copy their genetic code. When the EZH2 gene is active, the cell produces EZH2 protein. U-M scientists believe a future diagnostic test for high levels of this protein could serve as a red flag for physicians and help save the lives of men with the most dangerous form of the disease.
If additional research and human clinical trials confirm the results, a test for EZH2 protein could, for the first time, allow physicians to identify accurately those men who need immediate, aggressive treatment to prevent the cancer from spreading outside the prostate. Once prostate cancer metastasizes, or spreads, to other organs, it is usually incurable.
"Over the past 50 years, there has been no significant improvement in clinical outcome for men diagnosed with advanced prostate cancer and no way to tell ahead of time which cancers will spread and which cancers will remain localized," says Dr. Mark A. Rubin, a former U-M faculty member, who is now an associate professor of pathology at Brigham and Women's Hospital and director of the Dana Farber Harvard Cancer Center Tissue Microarray Core.
"It is exciting to think that we may have finally found something to help the 30,000 men who die every year from metastatic prostate cancer," he said.
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