Researchers studying the body's response to prostate cancer have developed a blood test for diagnosing the disease, and preliminary experiments suggest that it may be more reliable than the standard diagnostic blood test, the prostate-specific antigen (PSA) test.

The PSA test measures the blood levels of a single enzyme that is elevated in some men with the disease. But the levels can be elevated for reasons other than cancer, resulting in many biopsies that ultimately do not diagnose cancer.

The new test detects 22 proteins made by the immune system to fight the cancer. In a comparison, testing for the proteins was more accurate than PSA testing to correctly identify blood from prostate cancer patients while not misidentifying blood from a group of controls, according to findings in the September 22 New England Journal of Medicine.

"We view this study as a demonstration that screening blood for proteins produced in response to prostate cancer is a potential strategy for detecting the disease," says Dr. Arul Chinnaiyan of the University of Michigan Medical School in Ann Arbor, who led the study.

His team analyzed blood samples from 331 prostate cancer patients in the early stages of disease, and from 159 men with no history of cancer. Using a combination of technologies, they identified a "protein signature" for the disease.

The signature consists of 22 antitumor proteins known as "autoantibodies." All tumors produce abnormal proteins that are recognized by the immune system as foreign; the body responds by producing autoantibodies against them.

"Our strategy was to take advantage of the body's own immune system, which fights things that are foreign, like bacteria and viruses and cancer," says Dr. Chinnaiyan. The test is experimental and the results need to be validated, he adds.

Similar approaches have been used in other cancers to study individual autoantibodies. Last year, Dr. Chinnaiyan and his colleagues reported that some prostate cancer patients make autoantibodies against an enzyme called α-methylacyl-CoA racemase.

The new study defines a more representative collection, or panel, of autoantibodies, though the panel is a continual work in progress, notes Dr. Chinnaiyan. Efforts to define the autoantibodies for a given cancer characterize the emerging field of cancer immunomics.

A clinically validated panel, the researchers suggest, might be used in conjunction with PSA testing to help determine which patients truly need a biopsy to rule out a cancer diagnosis. The test could be given to patients who receive a positive PSA test but have not yet had a biopsy.

"We are cautiously optimistic, but there's a tendency to sensationalize results from early studies like this one," says Dr. James Montie, chairman of the Department of Urology at Michigan and a member of the research team.

He and others would certainly welcome a diagnostic test that is less vulnerable than the PSA test to confounding factors such as benign enlargement of the prostate.

Dr. Sudhir Srivastava, chief of NCI's Cancer Biomarkers Research Program and director of the Early Detection Research Network, which supported the study, is also optimistic. "I'm hopeful the results will be validated because the research was done so elegantly in terms of technology," he says.

"This is all part of continuing efforts to learn what goes wrong during prostate cancer and to identify biomarkers," says Dr. Srivastava. "The novelty comes from using the body's defense system to detect cancer rather than looking at, say, genetic mutations."

By Edward R. Winstead