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newly identified genetic marker may prove more accurate and more sensitive
than prostate-specific antigen in detecting prostate cancer A gene that triggers large-scale production of a specific protein in cancerous prostate cells may provide the basis for a more accurate and sensitive screening test than use of prostate-specific antigen, according to an article in the April 3rd issue of the Journal of the American Medical Association (JAMA). The investigators used advanced DNA microarray technology to identify the gene responsible for the protein, which is found in large amounts only in malignant cells and which is easily visualized when cells are stained. The protein is an enzyme involved in fat metabolism called a-methylacyl-CoA racemase, or AMACR. The enzyme had never previously been associated with any type of cancer, according to Mark A. Rubin, M.D., and Arul M. Chinnaiyan, M.D., Ph.D., the scientists who directed the current research study. "We detected high levels of [AMACR] protein in over 95 percent of more than 300 prostate tissue samples that contained localized cancer," says Chinnaiyan. "Equally important, we found no [AMACR] protein in benign prostate tissue or in tissue with non-malignant cell changes. We then evaluated the clinical utility of [AMACR] immunostaining on 94 prostate needle biopsies; the sensitivity and selectivity ratings were 97 percent and 100 percent." "[The protein AMACR] is one of approximately 20 genes which we found to be over-expressed consistently in prostate cancer," Chinnaiyan adds. "This doesn't mean that these genes cause prostate cancer, but they can be a marker or indicator of prostate cancer for diagnostic or prognostic purposes." The accuracy and specificity of immunostaining for the enzyme is a major improvement over the Prostate Specific Antigen test -- the only diagnostic screening test currently available to physicians. "The beauty [of AMACR] is that it is cancer-specific and found only in malignant cells," says Rubin. "Prostate specific antigen can't differentiate between cell changes caused by cancer and those caused by benign changes in the prostate. As a result, prostate specific antigen tests have a high rate of false positives, which can mean repeat needle biopsies and unnecessary surgery." Research on the genetic and molecular profile of prostate cancer using DNA microarray analysis is part of a major initiative underway at the researchers' center. Its goal is to link molecular genetics with clinical outcome for all types of cancer. "By looking at gene expression, we can learn so much more about a tumor," says cancer center director Max Wicha, M.D. "It explains why one patient's tumor remains localized, while another tumor spreads. It will allow us to tailor specific therapies to the gene expression profile of each patient." "Previous prostate cancer studies focused on one gene at a time," Chinnaiyan says. "With DNA microarray technology, we can look at thousands of genes in prostate cells simultaneously. This is important, because it is most likely that many genes are involved in the development and progression of prostate cancer -- each controlling a different step in the process." In previous work leading to the enzyme discovery, researchers analyzed more than 80 complementary DNA microarrays to assess gene expression profiles in four types of tissue. These included normal prostate tissue from men with and without prostate cancer, tissue with benign changes, localized prostate cancer and aggressive, metastatic cancer. Rubin and Chinnaiyan plan to
do enzyme assays in a much larger number of prostate tissue samples.
They are starting a prospective clinical trial to test the reliability
of testing against traditional surgical pathology diagnostic procedures.
Eventually, they hope to develop a blood test for the enzyme, eliminating
the need for needle biopsies of the prostate. |