ras gene mutations in salivary gland tumors

OBJECTIVE: To assess the prevalence of activating mutations in K-ras and H-ras genes in salivary gland tumors with ductal or acinar differentiation and to evaluate their potential correlation with clinical parameters. DESIGN: Paraffin-embedded tissue samples of salivary gland carcinomas were investigated by the application of a direct sequence analysis procedure with automated DNA sequencing of polymerase chain reaction-amplified ras sequences. SETTING: Tertiary care teaching hospital. PATIENTS: Twenty-four patients with salivary gland carcinoma were surgically treated. Nine had adenocarcinoma, 1 had adenosquamous carcinoma, 11 had mucoepidermoid carcinoma, and 3 had acinic cell carcinoma. RESULTS: Point mutations were detected in 7 (29%) of the 24 carcinomas examined. The K-ras gene was mutated in only 2 samples (8%): a GGC-to-ATC mutation at codon 13 in an adenocarcinoma and a GGC-to-GTC transversion mutation at codon 13 in a mucoepidermoid carcinoma. Five (21%) harbored H-ras mutations: 4 contained a GGC-to-GTC transversion mutation at codon 12 and 1 had 2 distinct mutations, the same G-to-T at codon 12 as was shown in the other cases and a GGT-to-GGA heterozygous mutation at codon 13. All the H-ras mutations were in the group of mucoepidermoid carcinoma lesions (45%; 5/11). CONCLUSION: Our data suggest that K-ras gene alteration is probably not an important factor in the oncogenesis of human salivary gland tumors. However, mutational activation of the H-ras gene appears to play a role in the development and/or progression of salivary gland mucoepidermoid carcinomas.