COX-2 expression in dysplasia of the head and neck: correlation with elF4E.
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.
Nathan
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CO
Department of Otolaryngology/Head & Neck Surgery, Louisiana State University Health Sciences Center and Veterans Administration Medical Center, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130, USA. cnatha@lsuhsc.edu
Leskov
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Lin
M
M
Abreo
F W
FW
Shi
R
R
Hartman
G H
GH
Glass
J
J
D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008565:Membrane Proteins; D011230:Precancerous Conditions / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases