Protein expression associated with prostate cancer progression

Decreased expression of a protein known as alpha-methylacyl-CoA racemase (AMACR) in localized prostate cancer may be associated with an increased rate of biochemical recurrence, suggest the findings of a multicenter study.

AMACR protein expression was determined by immunohistochemistry on two localized prostate cancer cohorts consisting of 204 men undergoing radical prostatectomy and 188 men undergoing watchful waiting. The endpoints for the cohorts were time to PSA failure and time to prostate cancer death, respectively.

A regression tree method and Cox proportional hazard models were used to determine protein expression cut points and effects of the cut points on prostate cancer outcome. Lower AMACR tissue expression was associated with worse prostate cancer outcome, independent of clinical variables (HR, 3.7 for PSA failure; p=.018; HR, 4.1 for prostate cancer death, p=.0006).

The risk of prostate cancer death was 18-fold higher among those with both low AMACR expression and a high Gleason score, and the AMACR cut point developed using prostate cancer-specific death as the endpoint predicted PSA failures independent of Gleason score, PSA, and margin status, reported lead author Mark A. Rubin, MD, of Brigham and Women's Hospital, Boston.

The study was published in Cancer Epidemiology, Biomarkers & Prevention (2005; 14:1424-32). A larger clinical trial including more than 1,300 Swedish men who have been diagnosed with cancer is now under way to confirm the findings.