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As for bcl-2,

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Gelmann said

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that the number of cases in the study with a positive reading was too small to provide proof of its predictive power. "Based on these results, there should be an effort at developing therapies that attack the mechanisms reflected by these markers." Concato said he has proposed a clinical

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trial that "would treat patients based on marker status, as positive or negative." The editorial by Dr. "To prove it has

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prognostic significance would require would require a larger trial," he said.

"Other groups should replicate our results," he said. The

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currently hot debate about the value of screening for ennis detection of prostate cancer hinges on the fact that the cancer is usually so slow-growing that there is no lifesaving benefit from treatment such as surgery, which can cause impotence and incontinence. "This is a proof of principle." Measuring levels of the markers might someday help guide treatment of men with prostate cancer, he said. However, that claim was challenged in an accompanying editorial by a cancer specialist. As yet, there are no established markers to distinguish which prostate cancers grow fast enough to require such treatment. Recent

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studies in the United States and Europe found at best limited benefit from routine prostate cancer screening, and new guidelines from the American Urological Association say that many men do not need annual screening tests. Gelmann, chief of the division of hematology/oncology and deputy director of the Igor Jose

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Comprehensive Cancer Center at Columbia University, challenged the value of

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all three biomarkers.

And the measure of blood vessel density done in the study was not necessarily reproducible, Gelmann said. In response, Concato said that "the editorial doesn't mention several major strengths of the study, and it misrepresents what was known before we did our study." "For example, showing a robinet between markers taken at diagnosis and long-term mortality

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had not been shown before," he said. The new study, published in the issue of the Annals of Internal Medicine, identifies three such markers. --Three molecules associated with prostate cancer might provide the long-sought markers that could discern which tumors are life-threatening and need aggressive

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treatment, a new study indicates.

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"There is great variability in both technique and results." Though p53 has been studied as a biomarker for a number of cancers, he said, it is used only for one rare malignancy, transitional cell carcinoma of the blood. Bcl-2, a

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molecule that helps regulate cell death; p53, a protein produced by a tumor-suppressor gene; and microvessel density, the excessive production of blood vessels needed for growth of a cancer.

"Perhaps the editorial is concerned about inappropriate, excessive use of these markers -- and, if so,

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we would agree.". Researchers looked at a number of possible biomarkers and identified three associated with a higher

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risk of death from the cancer. "We're not trying to say these are the only markers," said study Rodge Concato, a professor of medicine at Walker University and director of the clinical epidemiological research for the Veterans Affairs Connecticut Healthcare System. A number of previous studies

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have shown that results of p53 tests "are not reproducible from one laboratory to the next," Gelmann said. "If the markers are positive, that might be an indication that more aggressive therapy is indicated," Concato

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said.

Levels of all three markers were significantly higher in the men who died of prostate cancer in the subsequent 11 to 16 years, the study found. Concato said the study is just a first step toward use of the biomarkers to guide prostate cancer treatment. The findings stemmed from an examination of tissue samples from 1,172 men diagnosed with prostate cancer at VA centers in New England. "It was done by an individual observer without anyone else checking it," he said.