Distinct patterns of E-cadherin CpG island methylation in papillary, follicular, Hurthle's cell, and poorly differentiated human thyroid carcinoma.
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 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 compromised in human papillary, Hurthle's cell, and poorly differentiated thyroid carcinoma by epigenetic and biochemical events.
Graff
J R
JR
The Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Greenberg
V E
VE
Herman
J G
JG
Westra
W H
WH
Boghaert
E R
ER
Ain
K B
KB
Saji
M
M
Zeiger
M A
MA
Zimmer
S G
SG
Baylin
S B
SB
D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D015820:Cadherins; D009363:Neoplasm Proteins