title: Prevalence of KIT expression in human tumors.
abstract: OBJECTIVE
  KIT is a target for imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Gastrointestinal stromal tumors (GISTs) express KIT and respond favorably to imatinib therapy. To determine other tumors in which such a molecular targeted therapy might be indicated, we investigated KIT expression in different human tumor types. Because recent studies in GISTs suggest that KIT-activating mutations predict response to imatinib therapy, we also sequenced a subset of positive tumors.
  
  
  METHODS
  More than 3,000 tumors from more than 120 different tumor categories were analyzed by immunohistochemistry in a tissue microarray format. Seven commercially available anti-KIT antibodies were initially evaluated. The antibody A4502 (DAKO) was selected for analysis because of a high frequency of positivity in GIST and low staining background in other tissues. To determine the frequency of KIT mutations in various tumor types, the exons 2, 8, 9, 11, 13, and 17 (where mutations previously were reported) were sequenced in 36 tumors with strong KIT expression.
  
  
  RESULTS
  KIT positivity was detected in 28 of 28 GISTs (100%), 42 of 50 seminomas (84%), 34 of 52 adenoid-cystic carcinomas (65%), 14 of 39 malignant melanomas (35%), and eight of 47 large-cell carcinomas of the lung (17%), as well as in 47 additional tumor types. KIT mutations were found in six of 12 analyzed GISTs, but only in one of 24 other tumors.
  
  
  CONCLUSIONS
  The results suggest that KIT expression occurs infrequently in most tumor types and that, with the exception of GISTs, KIT gene mutations are rare in immunohistochemically KIT-positive tumors.
authors.affiliation: Institute of Pathology, University of Basel, Basel, Switzerland.
authors.forename: Philip Th
authors.initials: PT
authors.lastname: Went
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: Marcel
authors.initials: M
authors.lastname: Bundi
authors.forename: Martina
authors.initials: M
authors.lastname: Mirlacher
authors.forename: Peter
authors.initials: P
authors.lastname: Schraml
authors.forename: Sara
authors.initials: S
authors.lastname: Mangialaio
authors.forename: Sasa
authors.initials: S
authors.lastname: Dimitrijevic
authors.forename: Juha
authors.initials: J
authors.lastname: Kononen
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D046152:Gastrointestinal Stromal Tumors / Q000276:immunology* / Q000628:therapy; D020869:Gene Expression Profiling; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit