Human Thyroid Carcinoma Papillary, Follicular, Hurthle's Cell, and Poorly Differentiated Distinct Patterns of E-Cadherin CpG Island Methylation in

Expression of the invasion/metastasis suppressor, E-cadherin, is dimin ished or lost in thyroid carcinomas. Yet, mutational inactivation of I'.cadherin is rare. Herein, we show that this loss is associated with hypermethylation 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 com promised in human papillary, Hurthle's cell, and poorly differentiated thyroid carcinoma by epigenetic and biochemical events.