ras gene mutations in ethmoid sinus adenocarcinoma: prognostic implications.
BACKGROUND: The presence of mutations of the 3 ras proto-oncogenes in 31 cases of ethmoid sinus adenocarcinoma, an uncommon tumor type epidemiologically related to professional exposure to wood dust, was studied. METHODS: The authors studied 31 patients with ethmoid sinus adenocarcinoma. The polymerase chain reaction was used to amplify ras specific sequences of DNA isolated from paraffin embedded tumor samples. ras point mutations were subsequently detected with mutation specific oligonucleotide probes. RESULTS: H-ras was found to be mutated in 5 cases (16%). It is noteworthy that all of these mutations were identical and consisted of a G-for-T transversion at the second base of codon 12. H-ras mutations were related to a worse prognosis, with shorter tumor free survival (P = 0.04) and overall survival (P = 0.008). T classification was a significant clinical factor related to survival (P = 0.01 for disease free survival and P = 0.006 for overall survival). The prognostic value of H-ras mutation was consistent after adjustment for T classification. H-ras mutations showed no association with patients' previous exposure to wood dust. K-ras was found to be transformed in a single case; this was the only patient in the series to develop lymph node metastases. In this case, both the nasal tumor and the lymph nodes showed the GAT-for-GGT mutation at codon 12 of K-ras. No activation of the N-ras gene was detected. CONCLUSIONS: The presence of H-ras point mutations defines a subgroup of patients with ethmoid sinus adenocarcinomas for whom the prognosis is very poor. The finding that all of these mutations are identical emphasizes the peculiarity of this type of tumor.