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JNCI Journal of the National Cancer Institute 2004 96(11):834-843; doi:10.1093/jnci/djh145
© 2004 by Oxford University Press
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© 2004 Oxford University Press

ARTICLE

Humoral Immune Response to {alpha}-Methylacyl-CoA Racemase and Prostate Cancer

Arun Sreekumar, Bharathi Laxman, Daniel R. Rhodes, Srilakshmi Bhagavathula, Jason Harwood, Donald Giacherio, Debashis Ghosh, Martin G. Sanda, Mark A. Rubin, Arul M. Chinnaiyan

Affiliations of authors: Departments of Pathology (AS, BL, DRR, SB, JH, DG, AMC), Urology (MGS, AMC), Biostatistics (DG), and the Comprehensive Cancer Center (MGS, AMC), University of Michigan Medical School, Ann Arbor, MI 48109; Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115 (MAR)

Correspondence to: Arul M. Chinnaiyan, MD, PhD, Department of Pathology and Urology, University of Michigan Medical School, 1301 Catherine St., MSI 4237, University of Michigan, Ann Arbor, MI 48109-0602 (e-mail: arul{at}umich.edu)

Background: Although prostate-specific antigen (PSA) is a prototypic biomarker for prostate cancer, it has poor specificity. Expression of {alpha}-methylacyl-CoA racemase (AMACR), which is involved in the conversion of R-stereoisomers of branched-chain fatty acids to S-stereoisomers, has been shown to be specifically increased in prostate cancer epithelia. However, attempts to detect AMACR in circulation have not been successful. Hence, we determined whether an immune response to AMACR could be used as a serum biomarker for prostate cancer. Methods: Sera from patients with biopsy-proven prostate cancer and from control subjects were screened for a humoral immune response to selected tumor antigens, including AMACR, by using protein microarrays (46 patients, 28 control subjects). Humoral immune response to AMACR was then validated using high-throughput immunoblot analysis (151 patients, 259 control subjects) and enzyme-linked immunosorbent assay (ELISA) (54 patients, 55 control subjects). Receiver operating characteristic curves were used to determine the sensitivity and specificity of the immune response to AMACR to detect prostate cancer. Results: Immunoreactivity against AMACR was statistically significantly higher in sera from patients with prostate cancer than in control subjects by all three techniques (Pprotein microarray = .009, Pimmunoblot<.001, PELISA = .011). High-throughput immunoblot analysis revealed that, in subjects with intermediate PSA levels (4–10 ng/mL), the immune response against AMACR was more sensitive and specific than was PSA in distinguishing sera from prostate cancer patients relative to control subjects (sensitivity and specificity of 77.8% and 80.6% versus 45.6% and 50%, respectively; area under the curve of 0.789 versus 0.492; P<.001). Conclusion: Assays to detect a humoral immune response against AMACR may have the potential to supplement PSA screening in identifying patients with clinically significant prostate cancer, especially those with intermediate PSA levels.


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Editorial about this Article

Improved Biomarkers for Prostate Cancer: A Definite Need
H. Ballentine Carter and William B. Isaacs
J Natl Cancer Inst 2004 96: 813-815. [Extract] [Full Text] [PDF]



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