RESUMO
BACKGROUND: COX-2 inhibitors have shown promise in chemoprevention of epithelial 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 expressed in dysplasia of the head and neck and to study the correlation of expression 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 epithelium (n = 8), dysplasia (n = 51), mucosa adjacent to tumors (n = 11), and cancer of the head and neck (n = 19) using immunohistochemistry. In addition, 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 epithelium, 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 proportion of cases that expressed both molecular markers with increasing grades of dysplasia (P = 0.001). Western blot analysis showed increased expression of COX-2 and eIF4E in tumors compared with adjacent mucosa. All three HNSCC cell lines analyzed had increased expression of eIF4E, although only two had increased COX-2 expression. CONCLUSIONS: Expression of COX-2 in dysplasia suggested that COX-2 inhibitors 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 surrogate marker in chemoprevention trials.
