Cancer Res  1999 Sep 1;59(17):4297-300 

Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors.

Taniguchi M, Nishida T, Hirota S, Isozaki K, Ito T, Nomura T, Matsuda H,
Kitamura Y.

Department of Surgery I, Osaka University Graduate School of Medicine, Suita,
Japan.

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.

PMID: 10485475 [PubMed - indexed for MEDLINE]