Monteiro Alexandra, Gaspar Tiago Bordeira, Borges Inês, Canberk Sule, Pinto Mafalda, Pires Isabel, Soares Paula, Tavares Catarina
Cancer Signalling & Metabolism, i3S-Instituto de Investigação e Inovação em Saúde, 4200-135 Porto, Portugal.
Cancer Signalling & Metabolism, IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal.
Vet Sci. 2025 Jun 24;12(7):617. doi: 10.3390/vetsci12070617.
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 (, , , and ) 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 (human codon 600) or (human codon 61) regions. A 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.
甲状腺肿瘤在人类和猫中都很常见，最常见的是良性病变，而甲状腺癌在这两个物种中都很少被检测到。确定MAPK相关基因（ 、 、 和 ）的突变状态以及MAPK和mTOR通路的激活状态对于确定人类患者的诊断、治疗和预后至关重要。到目前为止，这些因素在猫甲状腺肿瘤发生中的作用仍未得到充分研究。本研究旨在阐明人类和猫甲状腺肿瘤之间潜在共享分子机制的存在及其意义。收集了15例福尔马林固定石蜡包埋的猫甲状腺上皮肿瘤（4例有异型性肿瘤和11例无异型性肿瘤）进行突变和免疫组化分析。针对人类同源热点的桑格测序显示 （人类密码子600）或 （人类密码子61）区域没有突变。在2例无滤泡型异型性的肿瘤中鉴定出一个错义突变（p.Gln232His）（2/15，13%）。无论突变状态如何，无异型性肿瘤中10/11（91%）的肿瘤免疫表达pERK（Thr202/Ty204），100%的肿瘤免疫表达pS6（Ser235/236），8/11（73%）的肿瘤免疫表达pAKT（Ser473）。pERK、pS6和pAKT的表达模式及其与临床病理特征的关联似乎反映了人类甲状腺肿瘤发生中观察到的进展动态。pAKT表达与同一甲状腺叶内多个肿瘤灶的存在相关，表明其可能作为猫甲状腺肿瘤侵袭性的标志物。本研究将猫引入作为人类甲状腺肿瘤发生的潜在动物模型，需要进一步研究来证实这种潜力。
