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c-KIT overexpression, without gene amplification and mutation, in paediatric renal tumours
  1. Chris Jones1,
  2. Maria Rodriguez-Pinilla2,
  3. Maryou Lambros2,
  4. Dorine Bax1,
  5. Boo Messahel1,
  6. Gordan M Vujanic3,
  7. Jorge S Reis-Filho2,
  8. Kathy Pritchard-Jones1
  1. 1
    Paediatric Oncology, Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, UK
  2. 2
    The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
  3. 3
    University of Wales Medical School, Cardiff, UK
  1. Dr Chris Jones, Paediatric Oncology, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK; chris.jones{at}icr.ac.uk

Abstract

Aims: To investigate the presence and prognostic relevance of KIT expression in paediatric renal tumours, and to determine whether receptor overexpression is associated with gene amplification and/or mutation.

Methods: Immunohistochemistry without antigen retrieval for CD117 was carried out on tissue microarrays consisting of 274 Wilms’ tumours, 13 clear cell sarcomas of the kidney (CCSK), 10 mesoblastic nephromas (MN), and 7 rhabdoid tumours of the kidney (RTK). In addition, gene copy number was investigated by chromogenic in situ hybridisation (CISH), and overexpressing tumours were sequenced for KIT mutations in exons 9, 11, 13 and 17.

Results: Only 8/200 (4.0%) Wilms’ tumours exhibited any degree of moderate–strong KIT staining in any of their assessable cell types. This small group of KIT-positive tumours had a shorter time to relapse (p = 0.0044, log-rank test). There were no positive MNs or RTKs; however 3/11 (27.3%) CCSKs were strongly positive, with an additional two cases weakly reactive. No cases exhibited gene amplification or mutation.

Conclusions: KIT overexpression in rare in Wilms’ tumours, although does appear to confer a worse prognosis, in particular for patients primarily treated with preoperative chemotherapy. CCSKs are associated with an increased expression of KIT, however, in the absence of gene amplification and/or activating mutation. The potential of anti-KIT therapeutic strategies in the treatment of paediatric renal tumours appears to be limited.

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Footnotes

  • Competing interests: None declared.

  • Abbreviations:
    CCSK
    clear cell sarcoma of the kidney
    CISH
    chromogenic in situ hybridisation
    GIST
    gastrointestinal stromal tumour
    MN
    mesoblastic nephroma
    RCC
    renal cell carcinoma
    RTK
    rhabdoid tumour of the kidney

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