COX-2 expression in dysplasia of the head and neck - Correlation with elF4E

BACKGROUND. COX-2 inhibitors have shown promise in chemoprevention of epith elial tumors. eIF4E is a biomarker that has identified individuals at high risk for relapse after definitive treatment for head and neck squamous cell cancer (HNSCC). Hence, the authors wanted to determine if COX-2 is express ed in dysplasia of the head and neck and to study the correlation of expres sion of COX-2 with eIF4E as a potential surrogate endpoint for determining response to COX-2 inhibitors. METHODS. The authors studied the expression of COX-2 and eIF4E in normal ep ithelium (n = 8), dysplasia (n = 51), mucosa adjacent to tumors (n = 11), a nd cancer of the head and neck (n = 19) using immunohistochemistry. In addi tion, Western blot analysis was performed on a subset of the above patient samples and HNSCC cell lines. RESULTS. Immunohistochemical analysis showed expression of COX-2 and eIF4E in all cancers and no expression in normal tissues. In dysplastic epitheliu m, there was a significant correlation between the expression of eIF4E and COX-2 for all groups of dysplasia combined (chi-square = 40.3, P < 0.001). A Cochran-Armitage trend test showed a significant increase in the proporti on of cases that expressed both molecular markers with increasing grades of dysplasia (P = 0.001). Western blot analysis showed increased expression o f COX-2 and eIF4E in tumors compared with adjacent mucosa. All three HNSCC cell lines analyzed had increased expression of eIF4E. although only two ha d increased COX-2 expression. CONCLUSIONS. Expression of COX-2 in dysplasia suggested that COX-2 inhibito rs may play a role in chemoprevention of head and neck cancers and that the correlation of Cox-2 with eIF4E indicates that eIF4E can be a potential su rrogate marker in chemoprevention trials. (C) 2001 American Cancer Society.