What is the pathophysiology of follicular thyroid carcinoma (FTC)?

Updated: Jun 18, 2020
  • Author: Luigi Santacroce, MD; Chief Editor: Neetu Radhakrishnan, MD  more...
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The molecular pathogenesis of follicular thyroid carcinoma (FTC) is thought to be initiated by point mutations that result in dysregulation of the phosphatidylinositol-3 kinase (PI3K)/AKT signaling pathway. Dysregulation of PI3K/AKT can be triggered by activating mutations in a variety of genes, including RAS, PIK3CA, and AKT1, as well as by inactivation of PTEN. [2]

Activating point mutations in RAS oncogenes are well known in follicular adenoma and carcinoma, [3, 4, 5] especially in poorly differentiated (55%) and anaplastic carcinoma (52%). Mutations in NRAS have been reported in 17% to 57% of FTCs; mutations in KRAS and HRAS are less often found. PAX8/PPARG gene fusion, which results in production of a PAX8-PPARγ fusion protein, has been identified in approximately one-third of FTC cases (range, 12% to 53%). Activating mutations in TERT, which encodes telomerase reverse transcriptase, have been described in about 15% of FTCs and are associated with the worst clinical features and prognosis. TSH receptor mutations have been found in 10.3% of FTC cases; these appear to be mutually exclusive with RAS mutations. [2]

A study of differential gene expression profiling of aggressive and nonaggressive follicular carcinomas identified 94 genes that distinguish follicular carcinomas from follicular adenomas (including PBP and CKS2) and 4 genes that distinguish aggressive follicular carcinomas from nonaggressive follicular carcinomas (NID2, TM7SF2, TRIM2, and GLTSCR2). [6]

Some molecules that physiologically regulate the growth of thyrocytes, such as interleukins (IL-1 and IL-8) or other cytokines (IGF1, TGF-beta, EGF) could play a role in the pathogenesis of FTC.


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