ras gene mutations in ethmoid sinus adenocarcinoma - Prognostic implications

BACKGROUND. The presence of mutations of the 3 ras proto-oncogenes in 31 ca ses of ethmoid sinus adenocarcinoma, an uncommon tumor type epidemiological ly 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 o f DNA isolated from paraffin embedded tumor samples. ms point mutations wer e subsequently detected with mutation specific oligonucleotide probes. RESULTS. H-ras was found to be mutated in 5 cases (16%). It is noteworthy t hat all of these mutations were identical and consisted of a G-for-T transv ersion at the second base of codon 12. H-ras mutations were related to a wo rse prognosis, with shorter tumor free survival (P = 0.04) and overall surv ival (P = 0.008). T classification was a significant clinical factor relate d 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 adj ustment for T classification. H-ms mutations showed no association with pat ients' 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 no de metastases. In this case, both the nasal tumor and the lymph nodes showe d 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 pa tients with ethmoid sinus adenocarcinomas for whom the prognosis is very po or. The finding that all of these mutations are identical emphasizes the pe culiarity of this type of tumor. Cancer 1999;86:255-64, (C) 1999 American C ancer Society.