title: Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors.
abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Gain-of-function mutations in the juxtamembrane domain of the c-kit gene have been found in several GISTs. In this study, we examined the correlation between the presence of c-kit mutation and prognosis in 124 cases of GIST. DNA samples were extracted from paraffin sections. Exon 11 of the c-kit gene encoding the juxtamembrane domain and exon 17 encoding the kinase domain were amplified by PCR and sequenced. Most GISTs (89%) express the KIT protein, and missense mutations of exon 11 were found in 71 of 124 GISTs (57%). No mutations were detectable in exon 17. These 71 mutation-positive GISTs were larger in size and had more frequently invaded adjacent tissues than did the 53 mutation-negative GISTs. Histologically, the mutation-positive GISTs showed higher mitotic figures and more necrosis and hemorrhage. The patients with mutation-positive GISTs showed more frequent recurrences (P = 0.0005) and higher mortality (P = 0.0001) than did those with mutation-negative GISTs. The c-kit mutation was an independent prognostic factor for overall and cause-specific survival of the patients with GISTs. These results suggest that GISTs may be divided into mutation-positive and -negative subtypes. The prognosis was worse in patients with mutation-positive GISTs than in those with mutation-negative GISTs. Thus, mutation of the c-kit gene may be a good prognostic marker of GISTs.
authors.affiliation: Department of Surgery I, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: T
authors.initials: T
authors.lastname: Nishida
authors.forename: S
authors.initials: S
authors.lastname: Hirota
authors.forename: K
authors.initials: K
authors.lastname: Isozaki
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
mesh_terms: D000595:Amino Acid Sequence; D003062:Codon; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D003062:Codon; D019009:Proto-Oncogene Proteins c-kit