Clinical prognosis in BRAF-mutated PTC.
BRAF mutation has recently emerged as a potential prognostic marker for papillary thyroid carcinoma (PTC) due to several studies suggesting that it may condition the development of tumors with aggressive behavior. A study of the phenotypes of thyroid follicular cell lines and transgenic mice characterized by targeted expression of BRAF mutation indicates that, at variance with RET/PTC rearrangement, it induces or facilitates genomic instability and higher invasiveness and eventually deeper tumor de-differentiation and more significant suppression of apoptosis. An analysis of differential gene expression of PTCs harboring BRAF mutation versus PTCs characterized by other genetic alterations shows an important impairment of the expression of genes related to intra-thyroidal iodine metabolism machinery, up-regulation of Glut-1 mRNA, methylation-induced gene silencing of tumor suppressor genes and up-regulation of pro-angiogenetic proteins such as VEGF. Correlation of BRAF mutation with PTC clinico-pathological features yields controversial results, with several studies showing the association with unfavourable clinico-pathological qualities, while others do not confirm the findings. This review will summarize the studies in favor of or in contrast with a role of BRAF mutation as a prognostic marker in PTC. We will also indicate what information we still need in order to routinely introduce this indicator in clinical practice.
Puxeddu
Efisio
E
Department of Internal Medicine, Center for Thyroid Proteomic and Genomic Research, University of Perugia, and Regional Oncology Referral Center, Santa Maria della Misericordia Hospital, Italy. efisio@dimisem.med.unipg.it
Moretti
Sonia
S
D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015321:Gene Rearrangement / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D017354:Point Mutation / Q000235:genetics*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D018631:ras Proteins / Q000235:genetics
D051096:Proto-Oncogene Proteins c-ret; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins