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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 11 4246-4252
Copyright © 1999 by The Endocrine Society


Original Studies

Fas (CD95) Expression is Up-Regulated on Papillary Thyroid Carcinoma1

Patricia L. Arscott, Theophil Stokes, Andrzej Myc, Thomas J. Giordano, Norman W. Thompson and James R. Baker Jr.

Departments of Internal Medicine (P.L.A., T.S., A.M., J.R.B.), Pathology (T.J.G.), and Surgery (N.W.T), University of Michigan, Ann Arbor, Michigan 48109

Address correspondence and requests for reprints to: James R. Baker, Jr., M.D., University of Michigan Medical Center, 1150 West Medical Center Drive, Room 9220 MSRB III, Ann Arbor, Michigan 48109-0648. E-mail: jbakerjr{at}umich.edu

Thyrocyte apoptosis signaled through the Fas receptor has been proposed as a mechanism for the cytotoxicity observed in thyroiditis, but the role the Fas pathway plays in thyroid cancer is not known. We examined Fas expression in thyroid tissue derived from patients with papillary carcinoma and follicular cancer. More intense immunohistological staining for the Fas protein was observed on papillary cancer cells as compared with adjacent normal follicles. To further characterize the expression of Fas in papillary cancer, paired normal and cancerous thyroid tissues were obtained at thyroidectomy from several donors, digested, and placed into cell culture. Messenger RNA was analyzed by ribonuclease protection assays, and protein was identified by flow cytometry. Fas expression was detected at levels up to 3-fold higher in cancerous thyrocytes compared with paired normal cells. To determine whether the expressed Fas antigen was functional, thyrocytes were treated with a monoclonal IgM anti-Fas antibody (clone CH11; Upstate Biotechnology, Inc., Lake Placid, NY) in the presence of interferon-{gamma} and cycloheximide. Whereas both normal and cancerous thyrocytes were induced to die after this treatment, the cancerous thyrocytes were more sensitive to anti-Fas antibody. This work demonstrates that the Fas antigen is expressed and functional on papillary thyroid cancer cells and this may have potential therapeutic significance.




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