The CD117 (KIT)
protein is overexpressed in many human
neoplasms including
adenoid cystic carcinoma of salivary glands. To evaluate the function of c-kit-activating mutations in
adenoid cystic carcinoma of the salivary gland, we studied 14 cases (13 primary, 1 cervical
lymph node metastasis) from our institution. KIT
protein expression was evaluated by immunohistochemistry using
formalin-fixed
paraffin-embedded tissue. Mutational analyses of c-kit extracellular (exon 9), juxtamembrane (exon 11) and
tyrosine kinase domains (exons 13 and 17) were performed by polymerase chain reaction, clonal selection and
DNA sequencing. All 14 cases demonstrated strong KIT expression by immunohistochemistry. Molecular analysis was successful in 8 of 14 cases, and c-kit missense point mutations were detected in seven of eight cases (88%) including seven in exon 11, two in exon 9, two in exon 13 and two in exon 17. Eight silent point mutations were detected in five cases. Two cases contained missense mutations in more than one exon. Different mutations were found in the primary
tumor and the cervical
lymph node metastasis of one patient. Point mutations in domains similar to those described in
gastrointestinal stromal tumors were detected, including Pro551Leu and Lys558Glu (5' end of exon 11), Leu576Phe (3' end of exon 11), Val643Ala (exon 13) and Asn822Ser (exon 17). Additional novel point mutations in exons 9, 11, 13 and 17 were also identified. This study is the first to report c-kit gene mutations in primary
adenoid cystic carcinoma of the salivary gland. Identification of such potential gain-of-function mutations in exon 11, and less frequently in exons 9, 13 and 17, suggests that KIT may be involved in the pathogenesis of
adenoid cystic carcinoma of salivary glands. Our study raises a prospect of correlation of c-kit mutation and a potential treatment of
adenoid cystic carcinoma with
tyrosine kinase inhibitor (
imatinib).