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Advances in Brief

α-Methylacyl-CoA Racemase

A New Molecular Marker for Prostate Cancer

Jun Luo, Shan Zha, Wesley R. Gage, Thomas A. Dunn, Jessica L. Hicks, Christina J. Bennett, Charles M. Ewing, Elizabeth A. Platz, Sacha Ferdinandusse, Ronald J. Wanders, Jeffrey M. Trent, William B. Isaacs and Angelo M. De Marzo
Jun Luo
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Shan Zha
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Wesley R. Gage
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Thomas A. Dunn
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Jessica L. Hicks
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Christina J. Bennett
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Charles M. Ewing
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Elizabeth A. Platz
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Sacha Ferdinandusse
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Ronald J. Wanders
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Jeffrey M. Trent
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William B. Isaacs
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Angelo M. De Marzo
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DOI:  Published April 2002
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    Fig. 1.

    Gene expression ratios for AMACR, GSTP1, and KRT8. Each colored square represents the relative mRNA abundance (ratio of sample:reference) in each sample compared with the common BPH reference. Each of the 12 normal samples (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) was paired with its matching cancer sample below the black line and the other 11 nonpaired cancer samples (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) positioned at the right side below the line. The measured expression ratios for each gene were presented graphically as colored squares, with the green squares representing higher expression in sample compared with the reference (BPH), the red squares meaning lower expression in sample than reference (BPH), and black squares indicating a ratio of ∼1. Color intensities are scaled according to the ratio (sample:reference) as shown at the bottom, with the brightest color having a ratio of >10 (green) or <0.1 (red).

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    Fig. 2.

    Western blot analysis of AMACR protein. Total tissue protein (25 μg) was analyzed using anti-AMACR antiserum. In A,pairs of tumor and corresponding normal tissue from 4 patients are designated by T1, T2, T3, T4, and N1, N2, N3, N4, respectively. For the second patient, there were two apparently independent tumors sampled (T2 and T2′). L, liver and K, kidney. In B, five different samples of BPH tissue (B1–B5) were analyzed together with a single sample of prostate cancer (T). The position of prestained molecular weight markers (ovalbumin at Mr 52,000 and carbonic anhydrase at Mr 37,000) is marked.

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    Fig. 3.

    IHC localization of AMACR in prostate tissue using standard slides. A, low-power image of Gleason pattern 3 carcinoma infiltrating between benign normal appearing glands (nl) showing homogeneous strong staining (×40). B, higher power view of representative region from A showing punctate cytoplasmic staining (×400). C, another case showing high-intensity staining in carcinoma (CaP), intermediate intensity staining in HGPIN (PIN), and no staining in normal (nl; ×100). D, higher power view of C showing strong staining in carcinoma glands (top left) and staining in acinus in that is involved partially with HGPIN with staining only in atypical HGPIN cells (PIN). Note negative staining in the normal appearing acinus just to the right of the carcinoma (×200).

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    Fig. 4.

    Relative expression of AMACR by IHC score in normal, HGPIN, and carcinoma by scoring of TMA spots. Box shows 25th-75th percentiles, as well as median (center line). Whiskers show 5th and 95th percentiles, and ovals represent outliers.

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    Fig. 5.

    Simultaneous single color localization of p63 and AMACR. Tissues were stained with a cocktail containing anti-p63 (nuclear) and anti-AMACR (punctate cytoplasmic) antibodies, and staining was localized simultaneously. In A, nuclear basal cell staining (p63) is apparent in normal appearing acinus. Arrows, infiltrating carcinoma cells (×100). B, higher power view of A. Arrowheads, nuclear basal cells staining (p63); arrow, carcinoma (×400). C, HGPIN showing moderate to weak punctate cytoplasmic AMACR staining and strong positive staining p63 staining of basal cells (×400). D, HGPIN (top gland) with weak cytoplasmic AMACR staining and nuclear basal cells staining (p63). Note small acinus apparently budding off (∗) of HGPIN gland showing very sparse basal cell nuclear staining (arrowhead). Below, there is moderate to weak intensity cytoplasmic staining in infiltrating carcinoma cells that lack p63 nuclear staining.

Tables

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  • Table 1

    AMACR IHC score from TMA analysis for 142 patients stratified by Gleason grade and pathological stage at radical prostatectomy

    GradeStage
    T2T3AT3BN1
    5–6n651220
    Median300268258Naa
    Mean255218258Na
    SD6810060Na
    7n241451
    Median293300243300
    Mean238263254300
    SD8360430
    8–9n51031
    Median300300283300
    Mean297274273300
    SD858340
    • a Na, not applicable.

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Cancer Research: 62 (8)
April 2002
Volume 62, Issue 8
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α-Methylacyl-CoA Racemase
Jun Luo, Shan Zha, Wesley R. Gage, Thomas A. Dunn, Jessica L. Hicks, Christina J. Bennett, Charles M. Ewing, Elizabeth A. Platz, Sacha Ferdinandusse, Ronald J. Wanders, Jeffrey M. Trent, William B. Isaacs and Angelo M. De Marzo
Cancer Res April 15 2002 (62) (8) 2220-2226;

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α-Methylacyl-CoA Racemase
Jun Luo, Shan Zha, Wesley R. Gage, Thomas A. Dunn, Jessica L. Hicks, Christina J. Bennett, Charles M. Ewing, Elizabeth A. Platz, Sacha Ferdinandusse, Ronald J. Wanders, Jeffrey M. Trent, William B. Isaacs and Angelo M. De Marzo
Cancer Res April 15 2002 (62) (8) 2220-2226;
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