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Cyclooxygenase-2 Expression in Thyroid Nodules

Departments of Surgery (M.C.S., O.N.T., M.H., D.G., L.T., T.J.F.), New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, New York 10021; and Strang Cancer Prevention Center (T.J.F.), New York, New York 10021

Address all correspondence and requests for reprints to: Thomas J. Fahey III, M.D., New York Presbyterian Hospital-Cornell University Room F-2024, 525 East 68 Street, New York, New York 10021. E-mail: tjfahey{at}mail.med.cornell.edu

Factors contributing to the development of thyroid neoplasia remain poorly understood. Recent evidence indicates that overexpression of the inducible cyclooxygenase, COX-2, is important 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 expression of COX-2 mRNA by quantitative RT-PCR. Immunoblotting and immunohistochemistry were performed on representative 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 specimens but not in the benign specimens. Additionally, COX-2 mRNA levels were significantly increased in malignant nodule samples compared with benign nodule samples. COX-2 protein expression was higher in 8 of 10 thyroid nodules compared with the adjacent tissue. Immunohistochemical analysis localized expression of COX-2 to the malignant epithelial cells. Immunofluorescence demonstrated COX-2 protein expression in all three thyroid cell lines. Finally, COX-2 expression 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.

This work was supported by the Alice Bohmfalk Charitable Trust (to T.J.F.).

Abbreviations: ARO, Anaplastic neoplasm; COX-1, constitutive cyclooxygenase; COX-2, inducible cyclooxygenase; FNA, fine needle aspiration; FRO, follicular neoplasm; NPA, papillary neoplasm; nt, nucleotide(s); PMA, phorbol 12-myristate 13-acetate.

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