Low Expression of Prostate Cancer Biomarker Tied to Progression, Death

NEW YORK JUN 07, 2005 (Reuters Health) - Alpha-methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer tissue compared with normal prostate tissues. However, low levels of AMACR are a powerful prognostic marker for prostate cancer progression and death from the disease, a new study shows.

In the June issue of Cancer Epidemiology, Biomarkers & Prevention, Dr. Mark A. Rubin of Harvard Medical School and colleagues describe "the development of a quantitative AMACR protein expression test to determine the risk of progression for men with clinically localized prostate cancer."

The investigators found that men with lower tissue levels of AMACR were 3.7 times more likely to have PSA failure and 4.1 times more likely to die of the disease, after adjustment for clinical characteristics such as Gleason score and tumor stage.

For men with low AMACR levels and high Gleason score, the risk of death from prostate cancer was 18 times greater.

"Future work will need to determine if this AMACR tissue test can be applied to prostate needle biopsies in a prospective manner to predict the risk of recurrence," Dr. Rubin and his team write.

The researchers determined the optimal AMACR cutpoint for differentiating prostate cancer outcomes by following 204 men who had undergone radical prostatectomy and 188 men being followed with watchful waiting. End points were time to PSA failure (increase of more than 0.2 ng/mL) and time to death from prostate cancer in the watchful waiting group.

The researchers found different AMACR cutpoints for cancer-specific death and biochemical failure, in line with past studies that suggested the latter may not be an optimal surrogate for clinical outcomes.

Evaluating biomarkers using tissue microarrays can be challenging, the researchers note. While the method used in the current study is "promising," they continue, its clinical application is still in the early stages.

They conclude: "This is the first study to show that AMACR expression is significantly associated with prostate cancer, and suggests that not all surrogate end points may be optimal to define biomarkers of aggressive prostate cancer."

SOURCE:

• Cancer Epidemiol Biomarkers Prev 2005;14:1-9.