Molecular characterization of kidney cancer

Association of hyaluronic acid family with histological subtypes and metastasis

Authors

  • Andrew Chi MD,

    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
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    • The first and second authors contributed equally and are joint first authors.

  • Samir P. Shirodkar MD,

    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
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    • The first and second authors contributed equally and are joint first authors.

  • Diogo O. Escudero BS,

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

    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
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  • Travis J. Yates BS,

    1. Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida
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  • Rajinikanth Ayyathurai MD,

    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
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  • Michael Garcia-Roig MD,

    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
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  • Jeffrey C. Gahan MD,

    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
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  • Murugesan Manoharan MD,

    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
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  • Vincent G. Bird MD,

    Corresponding author
    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
    • Vincent G. Bird, Department of Urology, University of Florida College of Medicine, PO Box 100247, Gainesville, FL 32610

      Vinata B. Lokeshwar, Department of Urology (M-800), University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL 33101

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  • Vinata B. Lokeshwar PhD

    Corresponding author
    1. Department of Urology, University of Miami School of Medicine, Miami, Florida
    2. Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida
    3. Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida
    • Vincent G. Bird, Department of Urology, University of Florida College of Medicine, PO Box 100247, Gainesville, FL 32610

      Vinata B. Lokeshwar, Department of Urology (M-800), University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL 33101

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  • We thank Drs. John Shields and Mohamed Aziz, University of Miami Miller School of Medicine, for their help in specimen collection.

Abstract

BACKGROUND:

Molecular profiling of renal cell carcinomas (RCCs) may improve the distinction between oncocytoma and malignant RCC subtypes and aid in early detection of metastasis. The hyaluronic acid (HA) family includes HA synthases (HAS1, HAS2, HAS3), hyaluronidases (HYAL-1, HYAL-2, HYAL-3, HYAL-4, PH20, HYAL-P1), and HA receptors (CD44s, CD44v, RHAMM). HA family members promote tumor growth and metastasis. The authors evaluated the expression of HA family members in kidney specimens.

METHODS:

By using quantitative polymerase chain reaction, mRNA levels of 12 HA family members were measured in tumor specimens obtained from 86 consecutive patients undergoing nephrectomy; 80 of them also provided normal specimens. Mean and median follow-up were 15.2 ± 8.8 and 13.8 months. RCC specimens included clear cell RCC: 65; papillary: 10; chromophobe: 5; oncocytoma: 6; metastasis positive: 17.

RESULTS:

Median HAS1, CD44s, and RHAMM transcript levels were elevated 3- to 25-fold in clear cell RCC and papillary and chromophobe tumors when compared with normal tissues. HYAL-4, CD44s, and RHAMM levels were elevated 4- to 12-fold in clear cell RCC and papillary tumors when compared with oncocytomas; only HYAL-4 levels distinguished between chromophobe and oncocytoma (P = .009). CD44s and RHAMM levels were significantly higher in tumors <4 cm (510 ± 611 and 19.6 ± 20.8, respectively) when compared with oncocytoma (46.4 ± 20 and 3.8 ± 2.5; P ≤ .006). In univariate and multivariate analyses, CD44s (P < .0001), RHAMM (P < .0001), stage, tumor size, and/or renal vein involvement were significantly associated with metastasis. The combined CD44s + RHAMM marker had 82% sensitivity and 86% specificity to predict metastasis.

CONCLUSIONS:

CD44s and RHAMM levels distinguish between oncocytoma and RCC subtypes regardless of tumor size and are potential predictors of RCC metastasis. Cancer 2012. © 2011 American Cancer Society.

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