Squamous cell carcinoma (SCC) stands as the second most prevalent skin cancer in dogs, primarily attributed to UV radiation exposure. Affected areas typically include regions with sparse hair and pale or depigmented skin. The significance of spontaneous canine cutaneous SCC as a model for its human counterpart is underscored by its resemblance. This study assesses the expression of key markers—Epidermal Growth Factor Receptor (EGFR), Cyclooxygenase-2 (Cox-2), and Ki-67—in canine cutaneous SCC. Our objective is to investigate the association between their expression levels and classical clinicopathological parameters, unraveling the intricate relationships among these molecular markers. In our retrospective analysis of 37 cases, EGFR overexpression manifested in 43.2% of cases, while Cox-2 exhibited overexpression in 97.3%. The EGFR, Cox-2 overexpression, and Ki-67 proliferation indices, estimated through immunohistochemistry, displayed a significant association with the histological grade, but only EGFR labeling is associated with the presence of lymphovascular emboli. The Ki-67 labeling index expression exhibited an association with EGFR and Cox-2. These findings propose that EGFR, Cox-2, and Ki-67 hold promise as valuable markers in canine SCC. EGFR, Cox-2, and Ki-67 may serve as indicators of disease progression, offering insights into the malignancy of a lesion. The implications extend to the potential therapeutic targeting of EGFR and Cox-2 in managing canine SCC. Further exploration of these insights is warranted due to their translational relevance and the development of targeted interventions in the context of canine SCC.

Cutaneous squamous cell carcinoma (SCC) is the second most common type of skin cancer in humans and one of the most frequent in dogs. Interest in studying this tumor type in animals has grown significantly, largely due to its high mutational load. Among the biomarkers, metalloproteinases (MMPs) have stood out. MMPs are a family of calcium- and zinc-dependent proteases that degrade the extracellular matrix (ECM), with MMP-9, a gelatinase, among the most investigated. MMP-9 expression has been reported to be increased in several tumors. The main objective of this study was to evaluate MMP-9 immunostaining in canine SCC. A descriptive analysis of MMP-9 expression was performed, categorizing it in tumor cells as absent, weak, moderate, or strong. In the SCC cases studied, with respect to marking intensity, 27 tumors showed strong intensity (+++), 6 moderate intensity (++), and 4 weak intensity (+). In all degrees of differentiation, a strong staining intensity predominated. In addition, we found MMP-9 expression in the stroma and macrophages, suggesting its role in tumor progression and in modulating the tumor microenvironment. These findings highlight the potential of MMP-9 as a prognostic biomarker. Understanding its role in SCC could significantly improve our ability to predict disease progression in dogs, leading to more effective treatment strategies.