Prostate cancer recurs in an estimated 15% to 30% of patients who have undergone a radical prostatectomy. One approach to identifying high-risk patients is to look for genes or protein biomarkers consistently overexpressed or underexpressed in prostate cancer tissue.
Daniel R. Rhodes, of the University of Michigan School of Medicine in Ann Arbor, Mark A. Rubin, M.D., of the Brigham and Women's Hospital and Harvard Medical School in Boston, and their colleagues used high-density tissue microarrays to examine the expression levels of 14 biomarkers from more than 2,000 prostate tumor samples to identify combinations of biomarkers that were most strongly associated with prostate cancer progression.
The samples were taken from 259 patients who underwent radical prostatectomy for localized prostate cancer. Recurrence was defined as a postsurgery prostate-specific antigen (PSA) level of more than 0.2 ng/mL (sometimes referred to as "biochemical recurrence").
The authors found that moderate or strong expression of EZH2, a transcriptional repressor, coupled with at most a moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was most strongly associated with biochemical recurrence of prostate cancer. They validated their findings in a training set of 103 patients, in a validation set of 80 patients, and in the combined set of 183 patients. The findings held even after adjusting for factors such as tumor stage and PSA level.
By the end of the study, 38% of the EZH2:ECAD-positive patients had experienced a recurrence, compared with 15% of the EZH2:ECAD-negative patients.
The authors conclude that EZH2:ECAD status may be valuable in determining the risk of prostate cancer progression, but more importantly, they say, the study illustrates the feasibility of using tissue microarrays to identify and validate combinations of molecular markers associated with prostate cancer progression. They note that future studies may identify additional molecular markers associated with prostate cancer progression.
In an accompanying editorial, Michael W. Kattan, Ph.D., of the Memorial Sloan-Kettering Cancer Center in New York, says that the finding may provide additional prognostic capability in the postoperative prostate cancer setting. But he cautions that markers should be judged on their ability to improve an already optimized prediction model.
"Continuous measurement of the improvement in our ability to predict outcomes for cancer patients helps us to know when prognostic progress has been made and keeps our focus on the important goal of improving our ability to predict patient outcome," he concludes.
Contact: Jeff Ventura, Brigham and Women's Hospital, 617-534-1600; fax: 617-534-1610, jventura@partners.org.
Editorial: Joanne Nicholas, Memorial Sloan-Kettering Cancer Center, 212-639-3573; fax: 212-639-3576, nicholaj@mskcc.org.
Rhodes DR, Sanda MG, Otte AP, Chinnaiyan AM, Rubin MA. Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer. J Natl Cancer Inst 2003;95:661–8.
Editorial: Kattan MW. Judging new markers by their ability to improve predictive accuracy. J Natl Cancer Inst 2003;95:634–5.
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.
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JNCI Journal of the National Cancer Institute