Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.
OBJECTIVE
Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial.


METHODS
We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced.


RESULTS
Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2).


CONCLUSIONS
The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.
Kim
Tae Won
TW
Section of Oncology/Hematology, Department of Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Lee
Hyoungnam
H
Kang
Yoon-Koo
YK
Choe
Mi Sun
MS
Ryu
Min-Hee
MH
Chang
Heung Moon
HM
Kim
Jung Sun
JS
Yook
Jeong Hwan
JH
Kim
Byung Sik
BS
Lee
Jung Shin
JS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D017154:Stromal Cells / Q000473:pathology
D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit