Cyclooxygenase-2 (cox-2) expression is an independent predictor of prostate cancer recurrence

Authors

  • Brian L. Cohen,

    1. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA
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    • Both the authors (BLC and PG) contributed equally to this work.

  • Pablo Gomez,

    1. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA
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    • Both the authors (BLC and PG) contributed equally to this work.

  • Yohei Omori,

    1. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA
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  • Robert C. Duncan,

    1. Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, USA
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  • Francisco Civantos,

    1. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA
    2. Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA
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  • Mark S. Soloway,

    1. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA
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  • Vinata B. Lokeshwar,

    1. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA
    2. Department of Cell Biology and Anatomy, Miller School of Medicine, University of Miami, Miami, FL, USA
    3. Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA
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  • Bal L. Lokeshwar

    Corresponding author
    1. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA
    2. Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA
    3. Department of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, USA
    • Department of Urology (M-800), P.O. Box 016960, Miami, FL 33101, USA
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    • Fax: 305-243-9724


Abstract

Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty-three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high- or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at ≥ 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process. © 2006 Wiley-Liss, Inc.

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