Study of morphological and molecular parameters with diagnostic and prognostic value in canine neoplasms

Abstract

Canine soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal neoplasms with overlapping histological features, historically considered as a single entity. Distinct histotypes, however, exhibit different biological behaviors, underscoring the need for detailed characterization using histology, immunohistochemistry, and molecular approaches. This study aimed to investigate three main aspects of canine STSs: (i) neoplastic cell proliferation, (ii) tumor immune microenvironment (TIME), and (iii) proteomic profiles of different STS types. Additional objectives included (iv) assessing the diagnostic utility of epithelial membrane antigen (EMA) in canine nerve sheath tumors and exploring the association of PDGFRβ expression with proliferation in intestinal leiomyosarcomas. Two studies examined neoplastic cell proliferation (i): the first confirmed the prognostic relevance of a Ki-67 cut-off of 56% in canine splenic hemangiosarcoma; the second found significant differences in the spatial distribution patterns of proliferative hotspots across different tumor types. Regarding TIME (ii), histotype-specific immune patterns were evidenced by immunohistochemistry: myxosarcomas elicited an immune response rich in M2 macrophages, B cells, and Tregs, whereas perivascular wall tumors were associated with a T-cell-rich, Treg-poor environment. The preliminary results of the proteomic profiling of canine STSs (iii), using LC-MS/MS, indicated clustering of certain histotypes (perivascular wall tumors and liposarcomas). In the additional studies (iv), EMA was widely expressed in both perivascular wall tumors and nerve sheath tumors, limiting its diagnostic utility, and PDGFRβ expression showed no statistically significant association with neoplastic cell proliferation in intestinal leiomyosarcoma, although PDGFRβ-positive cases had a higher Ki-67 labeling index. These findings increase the knowledge of the biology of canine STSs, highlighting histotype-specific differences in proliferation, immune response, and proteomic profiles, which may inform diagnosis, prognostication, and therapeutic strategies.