Protein Measures Prostate Cancer's Severity

A blood test could help doctors decide for or against surgery

TUESDAY, June 7, 2005 (HealthDay News) -- Researchers say they may be nearing a long-sought goal in prostate cancer therapy: a molecular marker that could distinguish between those men who need aggressive treatment, and those who will do well with watchful waiting.

A study of nearly 400 men diagnosed with prostate cancer found that low levels of a protein called alpha-methylacyl-Coa racemase (AMACR) were associated with worse outcomes over the next decade.

"We hope to eventually develop an easy serum blood test, similar to PSA, that will allow us to check for the presence and the amount of the biomarker to help direct treatment," said lead researcher Dr. Mark A. Rubin, chief of urologic pathology at Brigham and Women's Hospital in Boston.

The findings appear in the June issue of Cancer Epidemiology, Biomarkers & Prevention.

Tests for one blood marker, prostate-specific antigen (PSA), are now used to help detect prostate malignancy in its early stages. But doctors have found that many prostate cancers grow so slowly they require no more than watchful waiting, while others are quickly life-threatening. Unfortunately, right now there is no test that can tell which cancer requires surgery.

Such a test is needed to avoid unnecessary procedures, Rubin explained. "Statistics from recent studies suggest that we have to operate on 19 men to prevent one death, so obviously we are dramatically overtreating," he said. "The test we want would give more information to a clinician about who could be treated with just watchful waiting."

AMACR and its relationship to prostate cancer were discovered four years ago. Rubin, then at the University of Michigan, was the leader of a group that made one of the first reports on the molecule.

"When you look at prostate cancer, you look at the genes that are most highly expressed," he said. "This was one of the genes that came up as highly expressed in cancer cells but not normal cells."

The exact relationship of AMACR to prostate cancer is still unclear, but the relationship exists, Rubin said. In the study, the risk of death from prostate cancer for men with low AMACR levels and high Gleason scores -- another measure of prostate cancer severity -- was 18-fold greater than for men without those risk factors.

A lot has to be done before that finding can be put to use in medical practice, Rubin said. A necessary next step is to confirm the finding in a larger study, and that is being done. More than 1,300 men in Sweden who have been diagnosed with cancer are now being followed. That study, like the one just reported, is being conducted in collaboration with Swedish researchers.

Rubin also pointed out that as of now there is no blood test for AMACR -- current measurements utilize tissue samples. A blood test "would obviously be more useful," Rubin said. One possibility is a test that would measure the immune system's response to the presence of AMACR, and that is being explored, he added.

A member of Rubin's research team at the University of Michigan, Dr. Arul M. Chinnaiyan, said the new study's major strength is that it followed patients until death, as other studies have not done. "This might be one of the first tissue studies where you have death as an endpoint," he said.

Chinnaiyan said he is continuing to search for molecular markers that would guide clinical treatment of prostate cancer. "We have been focusing on markers that are up-rated by the disease, and on noninvasive ways of detecting them," he said.

More information

A comprehensive guide to prostate cancer is given by the National Cancer Institute.

SOURCES: Mark A. Rubin, M.D., chief, urologic pathology, Brigham and Women's Hospital, Boston; Arul M. Chinnaiyan, M.D., Ph.D, associate professor, pathology, University of Michigan, Ann Arbor; June 2005 Cancer Epidemiology, Biomarkers & Prevention
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