title: Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas.
abstract: Recent data suggested an increased frequency of KIT aberrations in mucosal melanomas, whereas c-KIT in most types of cutaneous melanomas does not appear to be of pathogenetic importance. However, studies investigating the status of the KIT gene in larger, well-characterised groups of patients with mucosal melanomas are lacking. We analysed 44 archival specimens of 39 well-characterised patients with mucosal melanomas of different locations. c-KIT protein expression was determined by immunhistochemistry, KIT gene mutations were analysed by PCR amplification and DNA sequencing of exons 9, 11, 13, 17 and 18. c-KIT protein expression could be shown in 40 out of 44 (91%) tumours in at least 10% of tumour cells. DNA sequence analysis of the KIT was successfully performed in 37 patients. In 6 out of 37 patients (16%) KIT mutations were found, five in exon 11 and one in exon 18. The presence of mutations in exon 11 correlated with a significant stronger immunohistochemical expression of c-KIT protein (P=0.015). Among the six patients with mutations, in two patients the primary tumour was located in the head/neck region, in three patients in the genitourinary tract and in one patient in the anal/rectal area. In conclusion, KIT mutations can be found in a subset of patients with mucosal melanomas irrespective of the location of the primary tumour. Our data encourage therapeutic attempts with tyrosine kinase inhibitors blocking c-KIT in these patients.
authors.affiliation: Department of Dermatology and Allergology, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany. satzger.imke@mh-hannover.de
authors.forename: I
authors.initials: I
authors.lastname: Satzger
authors.forename: T
authors.initials: T
authors.lastname: Schaefer
authors.forename: U
authors.initials: U
authors.lastname: Kuettler
authors.forename: V
authors.initials: V
authors.lastname: Broecker
authors.forename: B
authors.initials: B
authors.lastname: Voelker
authors.forename: H
authors.initials: H
authors.lastname: Ostertag
authors.forename: A
authors.initials: A
authors.lastname: Kapp
authors.forename: R
authors.initials: R
authors.lastname: Gutzmer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000201:enzymology*; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D044366:Transition Temperature
chemical_list: D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf