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The Oncology Center [J. R. G., J. G. H., S. B. B.] and Departments of Pathology [V. E. G., E. R. B., S. G. Z.] and Surgery [M. S., M. A. Z.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21231; L. P. Markey Cancer Center, Department of Microbiology and Immunology [V. E. G., E. R. B., S. G. Z.] and The Thyroid Cancer Research Laboratory, Veterans Affairs Medical Center and Department of Internal Medicine [K. B. A.], University of Kentucky Medical Center, Lexington, Kentucky 40536
Expression of the invasion/metastasis suppressor, E-cadherin, is diminished or lost in thyroid carcinomas. Yet, mutational inactivation of E-cadherin is rare. Herein, we show that this loss is associated with hyper-methylation of the E-cadherin 5' CpG island in a panel of human thyroid cancer cell lines. This aberrant methylation is evident in 83% of papillary thyroid carcinoma, 11% of follicular thyroid carcinoma, 40% of Hurthle's cell carcinoma, and 21% of poorly differentiated thyroid carcinomas. Contrary to previous reports, the majority of these poorly differentiated thyroid carcinomas express E-cadherin, but often within the cytoplasm rather than at the cell surface. Together, our data indicate that the invasion/metastasis suppressor function of E-cadherin is frequently compromised in human papillary, Hurthle's cell, and poorly differentiated thyroid carcinoma by epigenetic and biochemical events.
1 V. E. G., E. R. B., and S. G. Z. were supported by the Medical Center Research Fund and the McDowell Cancer Network, L. P. Markey Cancer Center, University of Kentucky. J. R. G., J. G. H., and S. B. B. were supported by NIH Grant CA43318, Oncor Corporation, and the Valvano Foundation (to J. G. H.). S. B. B. and J. G. H. receive research funding and are entitled to sales royalties from Oncor, which is developing products related to research described in this report. The terms of this arrangement have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies.
2 To whom requests for reprints should be addressed, at Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231.
Received 1/23/98. Accepted 3/30/98.
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