Abstract
Recently direct effects of T3 via the PI3K pathways have been described favoring differentiation and reducing thyroid growth. As thyroid carcinomas loose their ability to synthesize T3 any local thyroid hormone dependent effect rests on the uptake of thyroid hormones from the circulation. Here we investigated whether MCT8, a specific thyroid hormone transporter, is expressed in differentiated and undifferentiated thyroid carcinomas. A total of 157 papillary, 87 follicular, 61 anaplastic thyroid carcinomas were compared to 306 normal thyroids as to the expression of MCT8 by immunohistochemistry. 73 benign adenomas, 21 tissues from Hashimoto thyroiditis and 40 Graves thyroids served as additional controls. We evaluated MCT8 by 2 independent investigators as to their expression in the membrane or cytoplasm grading between 0 to 3. Membranous MCT8 expression was found in 34 % of normal thyroids. In autoimmune thyroid disease expression of MCT8 was slightly higher (Hashimoto thyroiditis 47.6%; Graves disease 47.5%). In benign adenomas interestingly MCT8 positivity in the membrane was clearly higher than in normal tissue and the percentage of strongly staining tissue was increased (60.3 % with positive staining). In differentiated thyroid carcinomas the numbers of membrane staining matched well the normal thyroids (PTC 21.7%, FTC 29.9 %) but there was an increased percentage of tumours with cytoplamatic staining. Contrasting to this finding only 3.3 % of anaplastic carcinomas stained positive in the membrane (mostly focally in few cells only) whereas at least a weak cytoplasmic staining was found in app. 50% of the tumours.
In summary, these data illustrate that MCT8 is expressed in normal thyroid and its expression is increased in differentiated thyroid carcinomas. This may form a basis for direct T3 related effects in thyroid carcinomas which are lost in parallel to the dedifferentiation in anaplastic tumours