title: Intratumoral FoxP3 expression is associated with angiogenesis and prognosis in malignant canine mammary tumors.
abstract: The activity of regulatory T cells (Tregs) is closely associated with the expression of FoxP3 transcription factor. FoxP3 regulatory T cells (FoxP3Treg) have immunosuppressive properties and can work for prevention of harmful autoimmune responses, however can also interfere with beneficial anti-tumor immunity. In human breast cancer these cells play a crucial role in tumor progression. In canine mammary tumors (CMT) this topic is not well-documented. This study included 80 malignant CMT and studied, by immunohistochemistry, the intratumoral FoxP3 expression together with microvessel density (MVD), vascular endothelial growth factor (VEGF) and several clinicopathological characteristics. Abundant FoxP3Treg cells were associated with tumor necrosis (p=0.001), high mitotic grade (p<0.001), more marked nuclear polymorphism (p=0.001), poor differentiation of tumors (p<0.001), high histological grade of malignancy (HGM) (p<0.001), presence of neoplastic intravascular emboli (p<0.001) and presence of lymph node metastasis (p<0.001). Intratumoral FoxP3 was correlated with MVD (r=0.827; p<0.001) and associated with VEGF (p=0.001). Additionally tumors with abundant FoxP3Treg cells were associated with shorter overall survival (OS) time in univariate and multivariate analysis (p<0.001 Kaplan-Meier curves and 7.97 hazard ratio, p<0.001 Cox proportional hazard model). Results suggest that Treg cells play a role in CMT progression and may contribute to increased angiogenesis and aggression in these tumors. The association of intratumoral FoxP3 expression with shorter OS in multivariate analysis suggests the usefulness of Treg cells as an independent prognostic marker.
authors: CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal; Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal.
authors: Maria Isabel
authors: MI
authors: Carvalho
authors: CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal; Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal.
authors: Isabel
authors: I
authors: Pires
authors: CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal; Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal.
authors: Justina
authors: J
authors: Prada
authors: Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal; Centro Hospitalar Veterinário, Rua Manuel Pinto de Azevedo 118, 4100-320 Porto, Portugal.
authors: Hugo
authors: H
authors: Gregório
authors: Hospital Veterinário do Porto, Travessa Silva Porto 174, 4250-475 Porto, Portugal; Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande, 376, 1749-024 Lisboa, Portugal; Center for the Study of Animal Sciences, CECA-ICETA, University of Porto, Portugal.
authors: Luis
authors: L
authors: Lobo
authors: Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal; Center for the Study of Animal Sciences, CECA-ICETA, University of Porto, Portugal; Center for Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal. Electronic address: fqueirog@utad.pt.
authors: Felisbina L
authors: FL
authors: Queiroga
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D004283:Dog Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D055806:Microvessels / Q000473:pathology; D009389:Neovascularization, Pathologic; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Canine mammary tumors; FoxP3T lymphocytes; Prognosis; Treg cells