HEX, PAX-8 and TTF-1 gene expression in human thyroid tissues: A comparative analysis with other genes involved in iodide metabolism

Objective: Benign and malignant thyroid tumours are characterized by alterations of the expression level of thyroid-specific genes involved in the iodide metabolism. Imbalance in the levels of transcription factors has been recognized as a critical molecular event in the development of neoplasm. The delineation of eventual correlations existing between the expression of transcription factors and of putative target genes in physiological and pathological conditions could be relevant to better understand tumorigenesis. Patients and methods: We examined the expression levels of transcription factors involved in thyroid development [thyroid transcription factor 1 (TTF-1), paired box gene 8 (PAX-8) and haematopoietically expressed homeobox (HEX)] in 101 thyroid tissues, including 14 normal thyroid tissues, 13 hyperfunctioning tissues, 27 benign adenomas and 47 follicular or papillary carcinomas. Then, we compared their expression levels with those of thyroid-specific genes involved in iodide metabolism. Results: In benign tumours, PAX-8 and TTF-1 gene expression levels were not significantly different from the expression levels in normal tissues. However, a significant decrease was found in carcinomas. Interestingly, HEX gene expression was significantly decreased in both hyper- and hypofunctioning benign tissues and also in carcinomas. Expression levels of Pendred syndrome (PDS), natrium iodine symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO) and dual oxidase 1 or 2 (DUOX2) genes were significantly correlated with the expression of PAX-8 and with that of HEX. Expression level of TTF-1 was weakly correlated only with the expression levels of PDS and DUOX2. Conclusion: Our findings suggest that alterations in the transcription factors PAX-8, TTF-1 and HEX gene expression, by acting individually or together, have a role in both thyroidal tumorigenesis and in the dedifferentiation process.