Identification of the JAK-STAT pathway in canine splenic hemangiosarcoma, thyroid carcinoma, mast cell tumor, and anal sac adenocarcinoma.

ABSTRACT

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.