Thyroid Cancer: State of Art of in Morocco

The majority of thyroid epithelial cells are follicular cells (named also thyrocytes), and their main function is thyroid hormone synthesis thanks to the follicular organization of thyrocytes, and to the expression of TPO (thyroperoxidase), Tg (thyroglobulin), NIS (sodium/iodide symporter) and the thyroid H2O2-generating NADPH oxidase DuOX2. Mutations in genes encoding for proteins involved in thyroid hormone synthesis has been reported in dyshormonogenic congenital hypothyroidism. Also, a large amount of H2O2 required for thyroid hormone biosynthesis, is suspected to be at the origin of thyrocyte transformation because H2O2 is considered as a potent DNA damaging agent.

Thyroid cancer is the commonest malignant endocrine tumour, and alarming increase in its incidence has been reported recently. Tumors derived from thyroid follicular cells display diverse neoplastic phenotypes, including benign follicular adenomas, follicular thyroid carcinomas (FTC), papillary thyroid carcinomas (PTC) and undifferentiated anaplasic thyroid carcinomas (ATC). PTC is the most frequent type according more than 80% of thyroid cancers. The main signalling pathway disturbed in thyroid cancer is the MAPK kinase pathway (RAS-RAF-MEK-ERK). 

Somatic alterations affecting the most common thyroid oncogenes (BRAF and RAS) and gene fusions involving essentially RET oncogene has been shown to activate constitutively this mitogenic pathway. BRAFV600E hot spot mutation found in 45% of PTCs, is also detected in undifferentiated ATC (20-40%), reinforcing the concept that BRAFV600E can lead to dedifferentiation and PTC can evolve to ATC with accumulation of additional mutations like p53 found only in poorly and undifferentiated thyroid carcinoma. However, the molecular mechanisms of thyroid carcinogenesis, tumors evolution and dedifferentiation as well as thyroid cancer etiology are not fully understood.