Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis

Authors

  • Mario W. Kramer MD,

    1. Department of Urology, Hannover Medical School (MHH), Hannover, Germany
    2. Department of Urology, University of Miami, Miller School of Medicine, Miami, Florida
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    • The first 2 authors contributed equally to this article.

  • Diogo O. Escudero BS,

    1. Department of Cell Biology and Anatomy, University of Miami, Miller School of Medicine, Miami, Florida
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    • The first 2 authors contributed equally to this article.

  • Soum D. Lokeshwar,

    1. Department of Urology, University of Miami, Miller School of Medicine, Miami, Florida
    2. Sylvester Comprehensive Cancer Center University, Miami School of Medicine, Miami, Florida
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  • Roozbeh Golshani PhD,

    1. Department of Cell Biology and Anatomy, University of Miami, Miller School of Medicine, Miami, Florida
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  • Obi O. Ekwenna MD,

    1. Department of Urology, University of Miami, Miller School of Medicine, Miami, Florida
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  • Kristell Acosta BS,

    1. Department of Urology, University of Miami, Miller School of Medicine, Miami, Florida
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  • Axel S. Merseburger MD,

    1. Department of Urology, Hannover Medical School (MHH), Hannover, Germany
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  • Mark Soloway MD,

    1. Department of Urology, University of Miami, Miller School of Medicine, Miami, Florida
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  • Vinata B. Lokeshwar PhD

    Corresponding author
    1. Department of Urology, University of Miami, Miller School of Medicine, Miami, Florida
    2. Department of Cell Biology and Anatomy, University of Miami, Miller School of Medicine, Miami, Florida
    • Division of Urology Research, Department of Urology (M-800), University of Miami, Miller School of Medicine, PO Box 016960, Miami, FL 33101
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    • Fax: (305) 243-6893


Abstract

BACKGROUND:

Cancer biomarkers are the backbone for the implementation of individualized approaches to bladder cancer (BCa). Hyaluronic acid (HA) and all 7 members of the HA family, that is, HA synthases (HA1, HA2, HA3), HYAL-1 hyaluronidase, and HA receptors (CD44s, CD44v, and RHAMM), function in tumor growth and progression. However, the diagnostic and prognostic potential of these 7 HA family members has not been compared simultaneously in any cancer. We evaluated the diagnostic and prognostic potential of HA family members in BCa.

METHODS:

Using quantitative PCR and immunohistochemistry, expression of HA family members was evaluated in prospectively collected bladder tissues (n = 72); mean and median follow-up were 29.6 ± 5.3 and 24 months, respectively. Transcript levels were also measured in exfoliated urothelial cells from urine specimens (n = 148).

RESULTS:

Among the HA family members, transcript levels of the HA synthases, HYAL-1, CD44v, and RHAMM were 4- to 16-fold higher in BCa tissues than in normal tissues (P < .0001); however, CD44s levels were lower. In univariate and multivariate analyses, tumor stage (P = .003), lymph node invasion (P = .033), HYAL-1 (P = .019), and HAS1 (P = .027) transcript levels, and HYAL-1 staining (P = .021) were independently associated with metastasis. Tumor stage (P = .019) and HYAL-1 (P = .046) transcript levels were also associated with disease-specific mortality. Although HA synthase and HYAL-1 transcript levels were elevated in exfoliated urothelial cells from BCa patients, the combined HAS2–HYAL-1 expression detected BCa with an overall sensitivity of 85.4% and a specificity of 79.5% and predicted BCa recurrence within 6 months (P = .004; RR = 6.7).

CONCLUSIONS:

HYAL-1 and HAS1 expression predicted BCa metastasis, and HYAL-1 expression also predicted disease-specific survival. Furthermore, the combined HAS2–HYAL-1 biomarker detected BCa and significantly predicted its recurrence. Cancer 2011. © 2010 American Cancer Society.

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