Utilization of Thyroid Transcription Factor-1 Immunostaining in the Diagnosis of Lung Tumors

Transcription factors play a crucial role in the determination and maintenance of differentiated cellular phenotype and their activity is considered to constitute the main switch to regulate gene expression (1 ). Based on their localization and expression, transcription factors have been subdivided into two major groups: ubiquitous and tissue-specific. Tissue-specific transcription factors are those that present in a few cell types and are involved in the regulation of genes expressed only in those cells. Thyroid transcription factor-1 (TTF-1) is a 38-kDa homeodomain containing nuclear transcription protein of the Nkx2 gene family. It consists of a single polypeptide of 371 amino acids that is encoded by a single locus (2 ). TTF-1 is expressed in the epithelial cells of the thyroid, lung, and diencephalon during early embryogenesis (3 –5 ). After birth, its expression is mostly maintained in the follicular and parafollicular C-cells of the thyroid and in bronchioalveolar cells. In the thyroid, TTF-1 activates the transcription of thyroglobulin, thyroperoxidase, and sodium-iodine transport protein (6 –8 ). In the lung, TTF-1 stimulates the synthesis of surfactant proteins A (9 ), B (10 ,11 ), and C (12 ), and Clara cell secretory protein (13 ) through the binding of the corresponding gene promoter enhancers. TTF-1 gene expression is regulated in respiratory epithelial cells at the transcriptional and posttranscriptional levels (14 ) by means of cross-regulatory mechanisms involving hepatocyte nuclear factor 3, Oct-1 protein, GATA-6, and calreticulin (15 –17 ).