TFF1 GENE-EXPRESSION IN HUMAN MEDULLARY-THYROID CARCINOMA

Medullary thyroid carcinoma (MTC) is an uncommon tumour of calcitonin- secreting C-cells of the thyroid gland, This cancer represents an impo rtant potential model for the study of mechanisms of human epithelial cell transformation. Although recent studies have identified the gene involved in familial forms of MTC, little is known about the molecular pathogenesis of the sporadic variants of this tumour. The biological and prognostic significance of TFF1 expression, particularly in divers e human malignancies, suggests that the TFF1 protein could have a role in human neoplasia, Furthermore, in prostate canter it has been demon strated that TFF1 expression is closely associated with premalignant c hanges and neuroendocrine differentiation. In the present study, the e xpression of TFF1 was analysed in 18 human MTCs, comprising sporadic a nd familial tumours, C-cell hyperplasia, and one case of lymph gland m etastasis, TFF1 expression was also examined in the cultures of a huma n MTC-derived tumour cell line (TT cell line). The results showed that ten sporadic tumours, three hereditary tumours (including C-cell hype rplasia). and one lymph gland metastasis displayed TFF1 immunoreactivi ty. Indirect fluorescence immunocytochemistry and Western blotting rev ealed that the TFF1 protein was strongly expressed in the TT cells. No rthern analysis revealed that tumours and TT cells expressed the TFF1 transcript. Although the function of TFF1 protein in the carcinogenesi s of MTC remains to be elucidated, its expression in the majority of c ases of both sporadic and hereditary tumours, metastatic tumours, and in C-cell hyperplasia suggests that it may contribute to the pathogene sis of MTC. (C) 1998 John Wiley & Sons, Ltd.