Vol. 9, Issue 12, Part B (2025)

The present study investigated the expression pattern and prognostic significance of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in spontaneous canine mammary gland tumors (CMGTs) using immunohistochemistry (IHC) and quantitative real-time PCR (qPCR). A total of 50 CMGT samples, comprising both benign and malignant forms, were analyzed to assess the relationship between CTLA-4 expression and tumor behavior. Immunohistochemical evaluation revealed variable CTLA-4 immunopositivity among tumor subtypes, with notably higher expression in aggressive variants such as carcinosarcoma and comedocarcinoma. qPCR analysis further confirmed a significant upregulation of CTLA-4 mRNA in malignant tumors compared to benign counterparts (p<0.05). Statistical analysis demonstrated that elevated CTLA-4 expression was strongly correlated with shorter overall survival (mean=174 days) and earlier tumor recurrence (mean=178 days), suggesting that CTLA-4 contributes to tumor progression through mechanisms of immune evasion. Moreover, CTLA-4 expression levels exhibited a positive association with higher histological grade and lymphatic invasion, emphasizing its role in tumor aggressiveness. Collectively, these results indicate that CTLA-4 serves not only as a marker of malignancy but also as a prognostic indicator in canine mammary tumors. The study provides foundational evidence supporting the potential use of CTLA-4 as a therapeutic target in canine oncology. Considering its parallel function in human breast cancer, these findings further underline the translational relevance of canine models for comparative oncology research. Targeting CTLA-4 through immune checkpoint blockade may represent a promising strategy for managing advanced or recurrent mammary tumors in dogs.