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June 12, 2002 |
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Protein test identifies aggressive prostate cancers MINNEAPOLIS / ST. PAUL-- June 12, 2002 (Cancer Digest) -- Can a simple test identify which patients have the most aggressive prostate cancers, even among patients whose tumors are at the same stage? Researchers think they may have come up with one that might also work for other cancers. The test developed by Dr. Akhouri Sinha, a professor of genetics at the University of Minnesota Cancer Center measures the ratio of two proteins produced by prostate cells, an enzyme called capthesin-B and an inhibitor of capthesin called stefin-A. In a study to be published in the June 15, 2002 issue of Cancer, the research team found that in tumors producing high levels of capthesin-B and low levels of stefin-A were more likely to spread, or metastasize, to nearby lymph nodes. Tumors with a balanced level of the two proteins or with higher levels of stefin-A than capthesin-B tended to grow more slowly. "The ratio of CB to stefin-A reveals differences in tumors that are not visible under the microscope," said Sinha. "If this test were done on tumors of newly diagnosed patients, we would have an indication of which cancers were most aggressive, and we could give those patients aggressive treatment. Those patients whose tumors show ratios of one, or less than one, may require less aggressive treatment. This approach could also be used for breast and colon cancer." The new test was developed by cancer researcher Sinha, and his colleagues in the laboratory of Dr. Donald Gleason, who developed the Gleason grading system, and is a co-author of the current study. The Gleason grading system assigns tumors a score between two and 10, with 10 being the most advanced cancer. Patients with a Gleason score from seven to 10 have a higher risk of dying of prostate cancer than those with lower scores, but some patients with higher scores outlive some with lower scores. While the Gleason score indicates the degree to which prostate cancers have progressed based on the shape and microscopic appearance of tumors, the grade does not tell how aggressively the tumors have been growing or metastasizing. "This means that within any score, there are biologically aggressive and less aggressive forms of cancer," said Sinha. "This makes it more difficult to predict outcomes for individual patients." In order to invade surrounding tissue and escape to blood vessels, cancer cells produce high levels of the enzyme cathepsin B (CB), which destroys proteins in the connective tissue that holds cells in place. But cells also produce natural inhibitors of CB called stefins. The researchers reasoned that prostate tumors in which levels of inhibitors were equal to or higher than CB would be less aggressive. But if CB was higher, the tumor would be more likely to spread. Working with prostate surgery samples from 97 prostate cancer patients and eight patients with a benign enlargement of the prostate, the researchers measured the ratio of CB to the inhibitor stefin-A in prostate tissue. They used tissue from Gleason grade 6 tumors, which appear relatively uniform in structure under the microscope. They found that the ratio of CB to stefin-A was significantly higher in patients whose cancer had spread to one or more pelvic lymph nodes than in patients whose nodes were clear. After skin cancer, prostate cancer is the most common form of cancer in U.S. men, according to National Cancer Institute statistics. More than a quarter of men diagnosed with cancer have prostate cancer. The disease strikes black men more often than white; Asian and American Indian men are affected less often. |
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