Investigation of angiogenesis and foxp3+ lymphocyte infiltrations in canine histiocytic tumors

Histiocytic proliferative disorders in dogs include reactive diseases such as cutaneous histiocytosis and systemic histiocytosis, and neoplastic disorders such as cutaneous histiocytoma, histiocytic sarcoma, and disseminated histiocytic sarcoma (malignant histiocytosis). In our study, it was aimed to evaluate the intensity of VEGF staining with FoxP3 positive T lymphocytes in various histiocytic diseases in dogs. Within the scope of the study, 23 cases diagnosed with histiocytic tumors were evaluated. Immunostaining with Iba-1, E-cadherin and CD3 antibodies was performed for differential diagnosis. As a result, lymphoma was diagnosed in 2 cases due to intense CD3 positivity. The diagnosis of histiocytic tumor was confirmed in 12 cases with intense Iba-1 positivity. In the other 9 cases, Iba-1 positive histiocytic cells were found to be infiltrated in the tumor tissue. As a result of histopathological examination of 12 Iba-1 positive cases, 4 cases were diagnosed as cutaneous histiocytoma, 3 cases as cutaneous histiocytosis and 5 cases as histiocytic sarcoma (1 haemophagocytic histiocytic sarcoma). E-cadherin positivity was found to be mild in only one cutaneous histiocytoma and one histiocytic sarcoma case. CD3 and FoxP3 positive T lymphocytes were counted and scored in 12 Iba-1 positive cases. In addition, varying degrees of positivity were observed in VEGF staining. As a result of statistical analyzes, a significant increase was observed in histiocytic sarcoma and cutaneous histiocytosis cases compared to cutaneous histiocytoma cases only in terms of CD3 positive score in group comparison. According to the correlation results of CD3, FoxP3 and VEGF scores, only a moderate negative correlation was observed between FoxP3 and VEGF. The results of the study suggest that the increase in the number of FoxP3 positive Tregs in canine histiocytic tumors may suppress tumor development by reducing VEGF-mediated angiogenesis.