Cyclooxygenase-2 Expression in Thyroid Nodules

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Abstract
Factors contributing to the development of thyroid neoplasia remain poorly understood. Recent evidence indicates that overexpression of the inducible cyclooxygenase, COX-2, is im- portant in the pathogenesis of epithelial carcinomas. These studies were undertaken to evaluate whether COX-2 is up- regulated in human thyroid neoplasia. Benign (n 14), and malignant (n 14) thyroid nodules were analyzed for expres- sion of COX-2 mRNA by quantitative RT-PCR. Immunoblot- ting and immunohistochemistry were performed on repre- sentative samples. Three human thyroid cancer cell lines were similarly analyzed for COX-2 expression. Levels of COX-2 mRNA were significantly increased in thyroid nodule samples compared with adjacent thyroid tissue in the malignant spec- imens but not in the benign specimens. Additionally, COX-2 mRNA levels were significantly increased in malignant nod- ule samples compared with benign nodule samples. COX-2 protein expression was higher in 8 of 10 thyroid nodules com- pared with the adjacent tissue. Immunohistochemical analy- sis localized expression of COX-2 to the malignant epithelial cells. Immunofluorescence demonstrated COX-2 protein ex- pression in all three thyroid cell lines. Finally, COX-2 expres- sion could be detected by RT-PCR in fine needle aspiration specimens of thyroid nodules. These data indicate that COX-2 is up-regulated in human thyroid cancer, but not in benign thyroid nodules, and suggest that COX-2 expression may serve as a marker of malignancy in thyroid nodules. (J Clin Endo- crinol Metab 87: 358 -363, 2002)

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