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Low AZGP1 expression predicts for recurrence in margin-positive, localized prostate cancer

Authors

  • Po Yee Yip,

    1. Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
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  • James G. Kench,

    1. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
    2. Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
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  • Krishan K. Rasiah,

    1. Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
    2. Department of Urology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
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  • Ruth Pe Benito,

    1. Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
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  • C.-Soon Lee,

    1. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
    2. Discipline of Pathology, School of Medicine, University of Western Sydney, Sydney, New South Wales, Australia
    3. Cancer Pathology, Bosch Institute, University of Sydney, Sydney, New South Wales, Australia
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  • Phillip D. Stricker,

    1. Department of Urology, St Vincent's Clinic, Darlinghurst, Sydney, New South Wales, Australia
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  • Susan M. Henshall,

    1. Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
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  • Robert L. Sutherland,

    1. Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
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  • Lisa G. Horvath

    Corresponding author
    1. Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
    2. Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
    • Sydney Cancer Centre, Royal Prince Alfred Hospital, Missenden Rd, Camperdown. NSW 2050, Australia.
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Abstract

BACKGROUND

Men with positive margins after radical prostatectomy (RP) for localized prostate cancer (PC) have a 40–50% biochemical relapse rate at 5 years. Adjuvant radiotherapy improves biochemical progression-free and overall survival in men with positive margins, but is associated with increased toxicity. There is an urgent need to identify new prognostic markers to define the group of patients who would benefit from multimodality therapy.

METHODS

Nuclear β-catenin, membranous secreted frizzled-related protein 4 (sFRP4), zinc-alpha 2-glycoprotein (AZGP1), and macrophage inhibitory cytokine-1 (MIC-1) have previously been identified as molecular markers of outcome in localized PC. From these published studies, we identified a subset of patients with positive margins. The aim of this study was to assess the association between these four molecular markers and outcome in men with margin-positive, localized PC.

RESULTS

We identified 186 men with positive margins from 330 men with localized PC; 53% had preoperative PSA >10 ng/ml, 72% extraprostatic extension (EPE), 24% seminal vesicles involvement (SVI), and 57% RP Gleason score ≥ 7. AZGP1 (P = 0.009), membranous sFRP4 (P = 0.03) and MIC-1 (P = 0.04) expression predicted for biochemical relapse on univariate analysis. Only absent/low AZGP1 expression (P = 0.01) was an independent predictor of recurrence in margin-positive, localized PC when modeled with preoperative PSA (P = 0.2), EPE (P = 0.2), SVI (P = 0.4), Gleason score ≥ 7 (P = 0.5) and adjuvant treatment (P = 0.4). Furthermore, there was an association between absent/low AZGP1 expression and clinical recurrence (P = 0.007).

CONCLUSIONS

AZGP1 is a potential molecular marker for biochemical relapse in men with margin-positive, localized PC. Routine assessment of this biomarker may lead to better selection of patients who will benefit from post-RP radiotherapy. Prostate 71:1638–1645, 2011. © 2011 Wiley-Liss, Inc.

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