Dysregulation of the Janus Kinase (JAK) - Signal Transducer and Activator of Transcription (STAT) cellular signaling pathway has been associated with the development and progression of multiple human cancers. STAT3 has been reported to be present and constitutively active in a number of veterinary cancers, and few studies have reported mutations or activation of JAK1 or JAK2. Archived tissue samples from 54 client-owned dogs with histologically-diagnosed HSA, MCT, TC, or AGASACA were evaluated by immunohistochemical scoring of JAK1, JAK2, STAT3, and the phosphorylated counterparts pJAK1, pJAK2, and pSTAT3. IHC scoring was retrospectively analyzed with retrospectively-collected clinical parameters, including patient characteristics, metastasis, and survival. JAK1, pJAK1, JAK2, pJAK2, STAT3, and pSTAT3 were present in all tumor types evaluated. Significant correlations between JAK 1/2 or STAT3 and activated or downstream components were identified in all tumor types. Clinically, pSTAT3 was correlated with development of metastasis in dogs with MCT, while increased JAK1 expression or activation may impact survival in dogs with MCT or HSA. These findings provide a foundation to further investigate the JAK-STAT pathway in canine malignancies for additional therapeutic options.

中文翻译：

---

犬脾血管肉瘤，甲状腺癌，肥大细胞瘤和肛门囊腺癌中JAK-STAT通路的鉴定。

Janus激酶（JAK）-信号转导子和转录激活子（STAT）细胞信号通路的失调与多种人类癌症的发生和发展有关。据报道，STAT3在许多兽医学癌症中存在并且具有组成性活性，很少有研究报道JAK1或JAK2发生突变或激活。通过免疫组化对JAK1，JAK2，STAT3和磷酸化对应物pJAK1，pJAK2和pSTAT3进行免疫组化评估，对54只具有组织学诊断的HSA，MCT，TC或AGASACA的客户拥有的狗的存档组织样本进行了评估。使用回顾性收集的临床参数（包括患者特征，转移和生存）对IHC评分进行回顾性分析。在评估的所有肿瘤类型中均存在JAK1，pJAK1，JAK2，pJAK2，STAT3和pSTAT3。在所有肿瘤类型中，都确定了JAK 1/2或STAT3与活化或下游成分之间的显着相关性。临床上，pSTAT3与MCT犬的转移发生有关，而JAK1表达或激活的增加可能会影响MCT或HSA犬的存活。这些发现为进一步研究犬恶性肿瘤中的JAK-STAT途径提供了基础，以寻求其他治疗选择。