title: Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: a multicenter study on 54 cases.
abstract: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms driven by oncogenic, mutational activation of KIT or platelet-derived growth factor receptor alpha (PDGFRA). GIST-specific KIT or PDGFRA mutations have been linked to tumor location, tumor cell morphology and clinical behavior. The purpose of this study was to evaluate the clinicopathologic profile of GISTs that have KIT exon 13 or exon 17 mutations. Through the collaboration of several GIST research groups, we gathered 54 cases from the pre-imatinib era that had such primary mutations. From our observations and those in the literature, we estimate that the frequency of these mutations is no higher than 1-2%. Almost all (32 of 33, 97%) of the KIT exon 13 mutations were the 1945A>G substitution leading to Lys642Glu. A majority (15 of 21, 71.4%) of the KIT exon 17 mutations were the 2487T>A substitution leading to Asn822Lys. Demographic and clinicopathologic data were available for 26 and 14 KIT exon 13 and exon 17 mutant GISTs, respectively. Median age and male to female ratio were similar to ones reported in other GIST studies. Small intestinal tumors were two times more frequent than gastric ones among KIT exon 17 mutants. Also, intestinal tumors were slightly overrepresented among KIT exon 13 mutants when compared with population-based studies. The majority of KIT exon 13 or exon 17 mutants had a spindle-cell morphology and only a few had epithelioid features. Tumor size varied from 1.2 to 25 cm and average mitotic rates were 9.5 and 4.2 for KIT exon 13 and exon 17 mutants, respectively. Gastric KIT exon 13 mutant GISTs tend to be slightly larger and more aggressive than gastric GISTs in average, whereas the behavior of small intestinal GISTs with KIT exon 13 mutations does not differ from other small intestinal GISTs. The latter is also true for all KIT exon 17 mutant GISTs.
authors.affiliation: Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA. lasota@afip.osd.mil
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lasota
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.forename: Sonja E
authors.initials: SE
authors.lastname: Steigen
authors.forename: Jerzy
authors.initials: J
authors.lastname: Stachura
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wozniak
authors.forename: Cristina
authors.initials: C
authors.lastname: Antonescu
authors.forename: Ondrej
authors.initials: O
authors.lastname: Daum
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Javier Garcia
authors.initials: JG
authors.lastname: Del Muro
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit