title: c-KIT overexpression, without gene amplification and mutation, in paediatric renal tumours.
abstract: OBJECTIVE
  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.
authors.affiliation: Paediatric Oncology, Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, UK. chris.jones@icr.ac.uk
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.forename: Maria
authors.initials: M
authors.lastname: Rodriguez-Pinilla
authors.forename: Maryou
authors.initials: M
authors.lastname: Lambros
authors.forename: Dorine
authors.initials: D
authors.lastname: Bax
authors.forename: Boo
authors.initials: B
authors.lastname: Messahel
authors.forename: Gordan M
authors.initials: GM
authors.lastname: Vujanic
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
mesh_terms: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002648:Child; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D020360:Neoadjuvant Therapy; D009392:Nephrectomy; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D018227:Sarcoma, Clear Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods; D009396:Wilms Tumor / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit