Artigos Originais, Revisões e Atualizações October 01, 2005 October 01, 2005

Pathogenesis of differentiated thyroid cancer (papillary and follicular)

DOI: 10.1590/S0004-27302005000500009

Differentiated thyroid cancers (papillary – PTC and follicular – FTC) are the most common endocrine malignancies. The recent progresses in the understanding of PTC and FTC pathogenesis are summarized in this review. In PTC, a single mutation of BRAF (the gene for the B-type Raf kinase) (V600E) is responsible for the disease in 40-50% of patients, especially in older people and is associated with a poorer clinicopathological outcome. Due to these characteristics, its use as a specific diagnostic and prognostic marker for PTC in cytological specimens is being implemented. Another important cause of PTC is rearrangements of the RET tyrosine kinase receptor (RET/PTC), which represent a recombination of the promoter and N-terminal domain of a partner gene with the C-terminal region of the RET gene, resulting in a chimeric gene with a protein product containing a constitutively activated RET tyrosine kinase, responsible for 20-30% patients, specially the younger or after radiation. The pathogenesis of FTC is less understood. A chromosomal translocation between the transcription factor PAX8 and the peroxisome proliferator-activated receptorg (PPARg) occurs in 30-50% of patients; however, the presence of PAX8-PPARg is also demonstrated in follicular adenomas. Therefore, there is no complete evidence that PAX8-PPARg is the cause of FTC. Another finding in FTC is mutations on the RAS gene, which excludes PAX8-PPARg rearrangements. Several genes, as TRg, PTEN, PKAR1A, DDIT3, ARG2, ITM1 and C1orf24 – some discovered by techniques of differential gene expression –, have been recently implicated in the pathogenesis of FTC.