Proliferation of the normal thyroid cell is regulated by stimulatory and inhibitory growth factors acting through their cognate cell surface receptors and subsequently through intracellular transduction pathways. In the normal adult gland, the balance of signals is such that proliferation is negligible. In the neoplastic cells, growth results from an irreversible disturbance of this equilibrium. Despite the apparent diversity of potential signal molecules that might theoretically be involved, it seems that only a small subset is capable of engendering tumor growth and is, therefore, selected in human thyroid neoplasia. Such proteins are coded for by genes RAS, RET, NTRK1 and TP53. The signal transducer ras is activated by point mutation and constitutes an early genetic alteration in tumors displaying a follicular histology. The genetic mechanisms for activation of growth factor receptor genes RET and NTRK1 are translocations or inversions in the papillary carcinomas and point mutations in the medullary carcinomas. Alterations of TP53 gene are reported in poorly differentiated and in most undifferentiated thyroid carcinomas suggesting that TP53 deregulation can play a significant role in the mechanism of dedifferentiation and progression of the disease. Although incomplete, the molecular model of thyroid carcinogenesis provides relevant tools for a better differential diagnosis and for the development of novel therapeutic avenues for such group of neoplasias.
Thyroid; Thyroid cancer; Oncogene; Tumor suppressor gene
