α-Methylacyl-CoA racemase expression and lethal prostate cancer in the Physicians' Health Study and Health Professionals Follow-up Study

Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
The Prostate (Impact Factor: 3.57). 02/2012; 72(3):301-6. DOI: 10.1002/pros.21432
Source: PubMed


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 nonsignificant trend for higher risk of lethal outcomes. The hazard ratio (HR) 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 HR 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.

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Available from: Preet K Dhillon, Mar 19, 2015
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    • "It has been reported that the abnormal expression of S100A12 is closely related with inflammation and vascular invasion of tumor cell [66], over inflammation and vascular invasion are closely related with tumor recurrence/metastasis. Meanwhile, the low expression of AMACR was independently associated with the development of metastasis and lethal in prostate cancer through regulating lipid metabolism and nuclear receptor activity [67]. Whether or not these reported functions are involved in the here reported HCC recurrence/metastasis needs further studies. "
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