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 expressio
n in thyroid tissue derived from patients with papillary carcinoma and foll
icular cancer. More intense immunohistological staining for the Fas protein
was observed on papillary cancer cells as compared with adjacent normal fo
llicles. 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 now cytometry. Fas expression was detected at levels up to 3-fold highe
r in cancerous thyrocytes compared with paired normal cells. To determine w
hether the expressed Fas antigen was functional, thyrocytes were treated wi
th a monoclonal IgM anti-Fas antibody (clone CH11; Upstate Biotechnology, I
nc., Lake Placid, NY) in the presence of interferon-gamma and cycloheximide
. Whereas both normal and cancerous thyrocytes were induced to die after th
is treatment, the cancerous thyrocytes were more sensitive to anti-Fas anti
body. This work demonstrates that the Fas antigen is expressed and function
al on papillary thyroid cancer cells and this may have potential therapeuti
c significance.