Fas ligand expression in thyroid carcinomas: A potential mechanism of immune evasion

Fas ligand (FasL) induces apoptosis by cross-linking the Fas receptor and is expressed by cells of the immune system. Recently, Fast was found in malignant tumors, suggesting that it helps them escape immune surveillance by eliminating infiltrating lymphocytes. We investigated the presence of Fast immunohistochemically in 48 thyroid carcinomas and by Western blotting and RT-PCR in 5 thyroid carcinoma cell lines. We found that in contrast to normal thyroid tissue, Fast was highly expressed in all papillary, follicular, and Huerthle carcinomas. Medullary carcinomas lacked or had minimal Fast expression. In papillary carcinomas, high levels of expression correlated independently with aggressive histology and unfavorable clinical presentation. Fast was also present in all thyroid cell lines. Thyroid carcinoma cells killed Fas-sensitive targets in a FasL-dependent manner in a coculture experiment. Cross-linking of Fas induced apoptosis in thyroid carcinoma cells only in the presence of cycloheximide. We conclude that Fast is specifically expressed in thyroid carcinomas of follicular epithelial origin, may help them evade the immune system, and may have prognostic implications in papillary carcinoma, as it is associated with a more aggressive phenotype. Thyroid carcinoma cells avoid Fas-mediated suicide possibly by expressing an inhibitor of the Fas apoptotic pathway.