Customize your JAMA Network experience by selecting one or more topics from the list below.
Rubin MA, Zhou M, Dhanasekaran SM, et al. α-Methylacyl Coenzyme A Racemase as a Tissue Biomarker for Prostate Cancer. JAMA. 2002;287(13):1662–1670. doi:10.1001/jama.287.13.1662
Author Affiliations: Departments of Pathology (Drs Rubin, Zhou, Dhanasekaran, Varambally, and Chinnaiyan and Mr Barrette), Urology (Drs Rubin, Sanda, Pienta, and Chinnaiyan), Internal Medicine (Dr Pienta), and Biostatistics (Dr Ghosh) and Comprehensive Cancer Center (Drs Rubin, Sanda, Pienta, and Chinnaiyan), University of Michigan Medical School, Ann Arbor.
Context Molecular profiling of prostate cancer has led to the identification
of candidate biomarkers and regulatory genes. Discoveries from these genome-scale
approaches may have applicability in the analysis of diagnostic prostate specimens.
Objectives To determine the expression and clinical utility of α-methylacyl
coenzyme A racemase (AMACR), a gene identified as
being overexpressed in prostate cancer by global profiling strategies.
Design Four gene expression data sets from independent DNA microarray analyses
were examined to identify genes expressed in prostate cancer (n = 128 specimens).
A lead candidate gene, AMACR, was validated at the
transcript level by reverse transcriptase polymerase chain reaction (RT-PCR)
and at the protein level by immunoblot and immunohistochemical analysis. AMACR levels were examined using prostate cancer tissue
microarrays in 342 samples representing different stages of prostate cancer
progression. Protein expression was characterized as negative (score = 1),
weak (2), moderate (3), or strong (4). Clinical utility of AMACR was evaluated using 94 prostate needle biopsy specimens.
Main Outcome Measures Messenger RNA transcript and protein levels of AMACR; sensitivity and specificity of AMACR as
a tissue biomarker for prostate cancer in needle biopsy specimens.
Results Three of 4 independent DNA microarray analyses (n = 128 specimens) revealed
significant overexpression of AMACR in prostate cancer
(P<.001). AMACR up-regulation
in prostate cancer was confirmed by both RT-PCR and immunoblot analysis. Immunohistochemical
analysis demonstrated an increased expression of AMACR
in malignant prostate epithelia relative to benign epithelia. Tissue microarrays
to assess AMACR expression in specimens consisting
of benign prostate (n = 108 samples), atrophic prostate (n = 26), prostatic
intraepithelial neoplasia (n = 75), localized prostate cancer (n = 116), and
metastatic prostate cancer (n = 17) demonstrated mean AMACR protein staining
intensity of 1.31 (95% confidence interval, 1.23-1.40), 2.33 (95% CI, 2.13-2.52),
2.67 (95% CI, 2.52-2.81), 3.20 (95% CI, 3.10-3.28), and 2.50 (95% CI, 2.20-2.80),
respectively (P<.001). Pairwise comparisons demonstrated
significant differences in staining intensity between clinically localized
prostate cancer compared with benign prostate tissue, with mean expression
scores of 3.2 and 1.3, respectively (mean difference, 1.9; 95% CI, 1.7-2.1; P<.001). Using moderate or strong staining intensity
as positive (score = 3 or 4), evaluation of AMACR protein expression in 94
prostate needle biopsy specimens demonstrated 97% sensitivity and 100% specificity
for detecting prostate cancer.
Conclusions AMACR was shown to be overexpressed in prostate
cancer using independent experimental methods and prostate cancer specimens. AMACR may be useful in the interpretation of prostate needle
biopsy specimens that are diagnostically challenging.
Create a personal account or sign in to: