Thyroid Transcription Factor � 1 (TTF-1) Immunoexpression in Thyroid Carcinoma with Follicular Origin

Abstract

Differentiated thyroid carcinomas are heterogeneous diseases with clinical and morphological features insufficient to predict their clinical behavior. The expression of tissue-specific transcription factors that control differentiated phenotype can be an additional method in evaluating the aggressiveness of a tumor, when differentiation markers and malignant phenotype of tumor cells are inconclusive. The expression of thyroid transcription factor-1 (TTF-1) is limited to thyroid follicular cells; it is a nuclear protein expressed in the epithelial cells of the thyroid, lungs and diencephalon. Using the monoclonal mouse antibody, clone 8G7G3/1, we examined the immunohistochemical expression of TTF-1 protein in 26 thyroid carcinomas (22 papillary carcinomas � PTC, 2 follicular carcinomas � FTC, 2 anaplastic carcinomas - AC), 4 follicular adenomas � FA, 10 benign thyroid lesions as underlying diseases (multinodular goiter � 3, Hashimoto thyroiditis � 3, Graves Basedow disease - 4) and sections of normal thyroid tissue, assessing the possible correlations with clinical and morphological features, as well as patient outcomes.TTF-1 nuclear expression was identified in 75% of benign thyroid lesions and 18/26 (69.23%) carcinomas. We noted TTF-1 nuclear expression in 68.18% of PTC (10% being associated with recurrent disease) and the absence of immunoreaction in 31.82% of PTC without recurrent disease. In patients with PTC, the risk of recurrence was significantly associated with the presence of nuclear TTF-1 expression in the primary tumor (p[0.001), but was not influenced by the type of surgery performed (p]0.05) or patients� age. TTF-1 nuclear expression did not correlate with patients� gender, tumor size, extent of disease at the moment of diagnosis and multifocal tumors (p]0.05). TTF-1 nuclear reactivity can be elevated in differentiated thyroid tumors (PTC and FTC) with aggressive clinical behavior that will develop recurrent or persistent disease. In anaplastic thyroid carcinomas with fast growth rate, immunoreactivity for TTF-1 and Ki-67 can offer useful information for tumor cell differentiation, while in the case of a mixed thyroid tumor it helps in distinguishing between well differentiated and undifferentiated/anaplastic areas.

Production of parathyroid-like cells from thyroid stem cells in co-culture environment

“…TTF1 is the protein that regulates transcription of thyroid cell-associated genes, and stains cell nuclei in brown color. [23,24] TTF1 is very useful in separating the thyroid from the parathyroid. [25] PTH staining is specific for parathyroid chief cells and produces brown cytoplasmic staining.…”