α-Methylacyl-CoA racemase (AMACR) is an enzyme that serves as a diagnostic biomarker of prostate cancer in clinical practice. Recent studies suggest that low AMACR expression is associated with biochemical recurrence and the development of fatal disease.
We conducted a prospective cohort study among 920 men aged 47–84 years, who were diagnosed with prostate cancer in the Physicians’ Health Study and the Health Professionals Follow-up Study cohorts, and whose resected tissue specimens were available for immunohistochemical analysis. We used Cox proportional hazards regression to evaluate the association of AMACR expression with lethal prostate cancer over a 20-year follow-up period.
In total, 68 men died from prostate cancer, and an additional 18 developed bony metastases during follow-up. We found that lower AMACR intensity was associated with higher prostate-specific antigen levels (p=0.003) and more advanced clinical stage (p=0.06) at diagnosis, and a non-significant trend for higher risk of lethal outcomes. The hazard ratio comparing the lowest to the highest quartile of AMACR expression intensity was 1.53 ((95% CI: 0.86, 2.73), p-for-trend across quartiles=0.07); this trend was further attenuated after adjustment for age, Gleason score, stage and cohort with a hazard ratio of 1.24 (95% CI 0.69, 2.22), p-for-trend=0.23.
Low AMACR expression in primary tumor specimens was not independently associated with the development of metastatic and lethal prostate cancer after treatment over a 20-year follow-up period, after adjustment for important clinical covariates at diagnosis.