Etiology and Pathogenesis

• Anaplastic thyroid carcinoma (ATC) accounts for 1.7% of all thyroid malignancies in the United States. 
• Women are more commonly affected than men.
• The majority of tumors are present in the seventh and eighth decades of life.
• It has a very poor prognosis:
  • Median survival of 5 months.
  • 1-year survival of 20%.

• ATC is typically thought to originate due to dedifferentiation of more differentiated thyroid cancers of follicular cell origin:
  • Up to 80% of ATCs occur in patients with preexisting goiters:
    • The process of dedifferentiation is complex and often involves changes in various chromosomal regions affecting cell cycle and other signal transduction pathways:
      • Several genes are known to be mutated in ATCs and include:
        • p53 (50% to 80%)
        • BRAF (20% to 40%)
        • RAS (20% to 40%)
        • PI3KCA (10% to 20%)
        • PTEN (5% to 15%)
        • AKT1 (5% to 10%)
        • CTNNB1 (5% to 60%). 

• Although some gene mutations are also commonly found in differentiated thyroid cancers (BRAF and RAS):
  • p53 tumor suppressor gene mutations are almost exclusively found in ATC.
    • Suggesting that they occur late in the dedifferentiation process.
• BRAF V600E mutations lead to constitutive activation of the MAPK pathway:
  • Resulting in tumor growth and reduction in the expression of the sodium-iodide symporter, which correlates with resistance to radioactive iodine (RAI) therapy.
• PIK3CA mutations result in aberrant activation of the PI3K/Akt/mTOR pathway and are found in more than 50% of ATCs and lead to increased growth.
• AKT1 (5% to 10%) mutations in particular also lead to resistance to conventional chemotherapeutic agents:
  • PTEN mutations also affect this pathway
• CTTNB1 encodes β-catenin:
  • A key member of the Wnt signaling pathway:
    • Causes tumor progression.
• Two ATC-specific mutations in the anaplastic lymphoma kinase gene lead to dual activation of the MAPK and PI3K/Akt pathways:
  • Which leads to multilayer and anchorage-independent tumor growth.
• Several microRNAs have also been reported to be dysregulated in ATC:
  • These include both upregulation (miRNA 222, 221, 146B, 106, 17 to 92) and downregulation (miRNA 618, 138, 125B, 30d, 26a)

 

Rodrigo Arrangoiz MS, MD, FACS cirujano de tumores de cabeza y cuello / cirugia endocrina miembro de Sociedad Quirúrgica S.C. experto en el manejo del cáncer de tiroides.

• Cumple con los requisitos determinados por el Dr. Ashok Saha para realizar cirugía de tiroides de manera efectiva y segura:

Entrenamiento:

• Cirugia general y gastrointestinal:

• Michigan State University:

• 2004 al 2010

• Cirugia oncológica / tumores de cabeza y cuello / cirugia endocrina:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Maestria en ciencias (Clinical research for healthprofessionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Cirugia de tumores de cabeza y cuello / cirugiaendocrina

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

http://www.sociedadquirurgica.com

http://www.hiperparatiroidismo.info

http://www.cirugiatiroides.com

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