title: α-Methylacyl-CoA racemase expression and lethal prostate cancer in the Physicians' Health Study and Health Professionals Follow-up Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. marcbarry@salud.unm.edu
authors.forename: Marc
authors.initials: M
authors.lastname: Barry
authors.forename: Preet K
authors.initials: PK
authors.lastname: Dhillon
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Tobias
authors.initials: T
authors.lastname: Kurth
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D019998:Racemases and Epimerases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase