α-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer

Mark A. Rubin, Ming Zhou, Saravana M. Dhanasekaran, Sooryanarayana Varambally, Terrence R. Barrette, Martin G. Sanda, Kenneth J. Pienta, Debashis Ghosh, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

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Abstract

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% Cl, 2.13-2.52), 2.67 (95% Cl, 2.52-2.81), 3.20 (95% Cl, 3.10-3.28), and 2.50 (95% Cl, 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% Cl, 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.

Original languageEnglish (US)
Pages (from-to)1662-1670
Number of pages9
JournalJournal of the American Medical Association
Volume287
Issue number13
StatePublished - Apr 3 2002

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Racemases and Epimerases
Coenzyme A
Prostatic Neoplasms
Biomarkers
Prostate
Needle Biopsy
Microarray Analysis
Staining and Labeling
Proteins
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Epithelium
Prostatic Intraepithelial Neoplasia
Genes
Sensitivity and Specificity
Regulator Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rubin, M. A., Zhou, M., Dhanasekaran, S. M., Varambally, S., Barrette, T. R., Sanda, M. G., ... Chinnaiyan, A. M. (2002). α-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. Journal of the American Medical Association, 287(13), 1662-1670.

α-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. / Rubin, Mark A.; Zhou, Ming; Dhanasekaran, Saravana M.; Varambally, Sooryanarayana; Barrette, Terrence R.; Sanda, Martin G.; Pienta, Kenneth J.; Ghosh, Debashis; Chinnaiyan, Arul M.

In: Journal of the American Medical Association, Vol. 287, No. 13, 03.04.2002, p. 1662-1670.

Research output: Contribution to journalArticle

Rubin, MA, Zhou, M, Dhanasekaran, SM, Varambally, S, Barrette, TR, Sanda, MG, Pienta, KJ, Ghosh, D & Chinnaiyan, AM 2002, 'α-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer', Journal of the American Medical Association, vol. 287, no. 13, pp. 1662-1670.
Rubin MA, Zhou M, Dhanasekaran SM, Varambally S, Barrette TR, Sanda MG et al. α-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. Journal of the American Medical Association. 2002 Apr 3;287(13):1662-1670.
Rubin, Mark A. ; Zhou, Ming ; Dhanasekaran, Saravana M. ; Varambally, Sooryanarayana ; Barrette, Terrence R. ; Sanda, Martin G. ; Pienta, Kenneth J. ; Ghosh, Debashis ; Chinnaiyan, Arul M. / α-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. In: Journal of the American Medical Association. 2002 ; Vol. 287, No. 13. pp. 1662-1670.
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abstract = "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{\%} Cl, 2.13-2.52), 2.67 (95{\%} Cl, 2.52-2.81), 3.20 (95{\%} Cl, 3.10-3.28), and 2.50 (95{\%} Cl, 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{\%} Cl, 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.",
author = "Rubin, {Mark A.} and Ming Zhou and Dhanasekaran, {Saravana M.} and Sooryanarayana Varambally and Barrette, {Terrence R.} and Sanda, {Martin G.} and Pienta, {Kenneth J.} and Debashis Ghosh and Chinnaiyan, {Arul M.}",
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T1 - α-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer

AU - Rubin, Mark A.

AU - Zhou, Ming

AU - Dhanasekaran, Saravana M.

AU - Varambally, Sooryanarayana

AU - Barrette, Terrence R.

AU - Sanda, Martin G.

AU - Pienta, Kenneth J.

AU - Ghosh, Debashis

AU - Chinnaiyan, Arul M.

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N2 - 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% Cl, 2.13-2.52), 2.67 (95% Cl, 2.52-2.81), 3.20 (95% Cl, 3.10-3.28), and 2.50 (95% Cl, 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% Cl, 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.

AB - 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% Cl, 2.13-2.52), 2.67 (95% Cl, 2.52-2.81), 3.20 (95% Cl, 3.10-3.28), and 2.50 (95% Cl, 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% Cl, 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.

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