Arul M. Chinnaiyan, M.D., Ph.D., and his American colleagues used advanced DNA microarray technology to show that the degree of overexpression of EZH2 was the highest among the 55 genes found to be more active in metastatic prostate cancer than in localized prostate cancer. Chinnaiyan noted that the current study is the first to link expression of EZH2 to biologic behavior of a solid tumor.

"We found the greatest EZH2 overexpression in metastatic prostate cancer tissue. At this point, it's unclear whether the gene plays a role in cancer's development or is simply an indicator of lethal progression," said Chinnaiyan.

The protein product of EZH2 is one of several related proteins that control a cell's genetic memory and interfere with transcription. According to Chinnaiyan, it is similar to a gene recently shown to halt transcription in fruit flies. If additional research and human clinical trials confirm the study findings, a test for EZH2 protein might enable physicians to identify men who need immediate, aggressive treatment to prevent metastasis.

"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 Mark A. Rubin, M.D. "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."

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 benign disease, and tissue with localized and advanced cancer. Four hundred of the tissue samples had been donated by patients who died from hormone-refractory metastatic prostate cancer.

"We never would have discovered this molecule without gene expression tumor profiles from these patients who donated their tissue," Rubin says. "We owe them a real debt of gratitude. Because of them, scientists now can study EZH2 and other important genes that some day will help other patients with prostate cancer."

"One of the differences in our study is that we correlated EZH2 expression in prostate cells with clinical outcome," Rubin explains. "We 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 prostate-specific antigen levels. We found EZH2 protein expression to be significantly better at predicting clinical outcome than any other factor."

The authors emphasized it is unlikely there will be just one biomarker for prostate cancer. In previous research, published in the April 3rd issue of the Journal of the American Medical Association, the same group described another protein (called AMACR), which is overexpressed in several types of cancer. The authors believe that a test for EZH2 expression, used in combination with screening tests for AMACR and other biomarkers, could help physicians diagnose cases of prostate cancer earlier and determine the most effective and least invasive treatment for each individual patient.