Exploring MAPK and mTOR Pathways in Feline Thyroid Tumors
2025
Alexandra Monteiro | Tiago Bordeira Gaspar | Inês Borges | Sule Canberk | Mafalda Pinto | Isabel Pires | Paula Soares | Catarina Tavares
Thyroid tumors are common in humans and cats, occurring most commonly as benign lesions, whereas thyroid carcinoma is barely detected in both species. Determining the mutational status of MAPK-related genes (BRAF, NRAS, HRAS, and KRAS) and the activation status of MAPK and mTOR pathways is crucial for establishing the diagnosis, treatment, and prognosis of human patients. So far, the role of such players in feline thyroid tumorigenesis remains underexplored. This study aims to elucidate the presence and implications of potential shared molecular mechanisms between human and feline thyroid tumors. Fifteen formalin-fixed paraffin-embedded feline thyroid epithelial tumors (four tumors with atypia and 11 with no atypia) were collected to perform mutational and immunohistochemical analyses. Sanger sequencing targeting human homologous hotspots revealed no mutations in BRAF (human codon 600) or RAS (human codon 61) regions. A KRAS missense mutation (p.Gln232His) was identified in two tumors with no atypia of follicular pattern (2/15, 13%). Regardless of the mutational status, pERK (Thr202/Ty204) was immuno-expressed in 10/11 (91%), pS6 (Ser235/236) in 100%, and pAKT (Ser473) in 8/11 (73%) of the tumors with no atypia. The expression patterns of pERK, pS6, and pAKT and their associations with clinical-pathological features seem to mirror the progression dynamics observed in human thyroid tumorigenesis. pAKT expression was associated with the presence of multiple tumor foci within the same thyroid lobe, suggesting its potential as a marker of aggressiveness in feline thyroid tumors. This study introduces cats as potential animal models for human thyroid tumorigenesis, with further research required to confirm such potential.
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