[Pathogenesis of differentiated thyroid cancer (papillary and follicular)].
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 receptorgamma (PPARgamma) occurs in 30-50% of patients; however, the presence of PAX8-PPARgamma is also demonstrated in follicular adenomas. Therefore, there is no complete evidence that PAX8-PPARgamma is the cause of FTC. Another finding in FTC is mutations on the RAS gene, which excludes PAX8-PPARgamma rearrangements. Several genes, as TRgamma, PTEN, PKAR1A, DDIT3, ARG2, ITM1 and C1orf24--some discovered by techniques of differential gene expression--, have been recently implicated in the pathogenesis of FTC.
Maciel
Rui M B
RM
Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP. rmbmaciel-endo@pesquisa.epm.br
Kimura
Edna T
ET
Cerutti
Janete M
JM
D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*
D009363:Neoplasm Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D048493:Proto-Oncogene Proteins B-raf