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Exploring MAPK and mTOR Pathways in Feline Thyroid Tumors.

Alexandra Monteiro1,2,3, Tiago Bordeira Gaspar1,2,4,5, Inês Borges5

  • 1Cancer Signalling & Metabolism, i3S-Instituto de Investigação e Inovação em Saúde, 4200-135 Porto, Portugal.

Veterinary Sciences
|July 25, 2025
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Summary

Feline thyroid tumors share molecular pathways with human counterparts, with KRAS mutations and activated MAPK/mTOR pathways observed. These findings suggest cats may serve as valuable models for studying human thyroid cancer progression.

Keywords:
MAPKPCRcatsimmunohistochemistrymTORthyroid neoplasms

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Area of Science:

  • Comparative oncology
  • Molecular pathology
  • Translational research

Background:

  • Thyroid tumors are common in humans and cats, often benign, with limited understanding of molecular drivers in feline thyroid tumorigenesis.
  • Investigating shared molecular mechanisms between human and feline thyroid tumors is crucial for advancing diagnosis and treatment.

Purpose of the Study:

  • To investigate the mutational status of MAPK-related genes and the activation of MAPK and mTOR pathways in feline thyroid tumors.
  • To explore potential shared molecular mechanisms between human and feline thyroid tumorigenesis.

Main Methods:

  • Analysis of 15 feline thyroid epithelial tumors using Sanger sequencing and immunohistochemistry.
  • Targeted sequencing of BRAF and RAS hotspots, alongside assessment of pERK, pS6, and pAKT expression.

Main Results:

  • No BRAF or RAS (codon 61) mutations were detected. A KRAS mutation (p.Gln232His) was found in 13% of tumors.
  • High expression of pERK (91%), pS6 (100%), and pAKT (73%) was observed in tumors without atypia.
  • pAKT expression correlated with multiple tumor foci, suggesting potential as an aggressiveness marker.

Conclusions:

  • Feline thyroid tumors exhibit activated MAPK and mTOR pathways, similar to human thyroid cancer.
  • The identified KRAS mutation and pathway activations suggest shared tumorigenesis mechanisms.
  • Cats may serve as a valuable animal model for human thyroid cancer research.