TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlatio...

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Main Authors: Maria Isabel Carvalho, Ricardo Silva-Carvalho, Justina Prada, Carla Pinto, Hugo Gregório, Luis Lobo, Isabel Pires, Felisbina L. Queiroga
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Veterinary Quarterly
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Online Access:https://www.tandfonline.com/doi/10.1080/01652176.2024.2390941
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author Maria Isabel Carvalho
Ricardo Silva-Carvalho
Justina Prada
Carla Pinto
Hugo Gregório
Luis Lobo
Isabel Pires
Felisbina L. Queiroga
author_facet Maria Isabel Carvalho
Ricardo Silva-Carvalho
Justina Prada
Carla Pinto
Hugo Gregório
Luis Lobo
Isabel Pires
Felisbina L. Queiroga
author_sort Maria Isabel Carvalho
collection DOAJ
description Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGFβ were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGFβ were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGFβ expression and with concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGFβ and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.
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spelling doaj-art-9dcc46300afa4ae9b7d7aa1ea2ba25a52025-08-20T02:50:37ZengTaylor & Francis GroupVeterinary Quarterly0165-21761875-59412024-12-0144111210.1080/01652176.2024.2390941TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic roleMaria Isabel Carvalho0Ricardo Silva-Carvalho1Justina Prada2Carla Pinto3Hugo Gregório4Luis Lobo5Isabel Pires6Felisbina L. Queiroga7MVET Research in Veterinary Medicine. Faculty of Veterinary Medicine, Lusófona University – Lisbon Centre, Lisboa, PortugalCEB – Centre of Biological Engineering, University of Minho, Braga, PortugalVeterinary and Animal Research Center (CECAV), University of Trás-os-Montes and Alto Douro, Vila Real, PortugalDepartment of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, PortugalAnicura Centro Hospitalar Veterinário, Porto, PortugalMVET Research in Veterinary Medicine. Faculty of Veterinary Medicine, Lusófona University – Lisbon Centre, Lisboa, PortugalVeterinary and Animal Research Center (CECAV), University of Trás-os-Montes and Alto Douro, Vila Real, PortugalVeterinary and Animal Research Center (CECAV), University of Trás-os-Montes and Alto Douro, Vila Real, PortugalTransforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGFβ were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGFβ were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGFβ expression and with concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGFβ and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.https://www.tandfonline.com/doi/10.1080/01652176.2024.2390941Angiogenesiscanine mammary tumorsCD31FoxP3prognosisTGFβ
spellingShingle Maria Isabel Carvalho
Ricardo Silva-Carvalho
Justina Prada
Carla Pinto
Hugo Gregório
Luis Lobo
Isabel Pires
Felisbina L. Queiroga
TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role
Veterinary Quarterly
Angiogenesis
canine mammary tumors
CD31
FoxP3
prognosis
TGFβ
title TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role
title_full TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role
title_fullStr TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role
title_full_unstemmed TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role
title_short TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role
title_sort tgfβ in malignant canine mammary tumors relation with angiogenesis immunologic markers and prognostic role
topic Angiogenesis
canine mammary tumors
CD31
FoxP3
prognosis
TGFβ
url https://www.tandfonline.com/doi/10.1080/01652176.2024.2390941
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