Tumores mamários caninos: relação da versikina com o perfil linfocítico e o microambiente tumoral

Abstract

Two separate experiments were performed using bitches with mammary carcinoma to evaluate the expression of VKINA in the tumor microenvironment and its possible correlation with the lymphocytic response and disease outcome in bitches with malignant mammary tumors. In the first experiment, 65 bitches were divided into four groups: control (CG: n=13), mammary carcinomas (CM: n=12), carcinomas in mixed tumors (CMT: n=33), and carcinosarcomas (CSS: n=7). The patients underwent clinical and laboratory evaluation, mastectomy, clinical-pathological characterization of the tumor, morphology of the inflammatory infiltrate, immunohistochemistry with VKINA staining, and immunophenotyping of peripheral blood and tumors by flow cytometry, in addition to survival analysis. The results indicate that in malignant mammary tumors of bitches there is an intratumoral predominance of TCD4+ lymphocytes about TCD8+ lymphocytes. In contrast, tumors with higher expression of TCD8+ presented a better prognosis. High expression of VKINA (≥120) directly correlated with histological grading and TGFβ+ but cannot yet be considered an independent prognostic marker. In conclusion, high expression of VKINA (≥120) may interfere with tumor aggressiveness, and the study of its interactions may help in understanding its immunomodulatory capacity, especially in different histological types, bringing new prognostic and therapeutic perspectives, both for female dogs and for women. In the second experiment, a total of 46 female dogs were selected and divided into three groups: control (GC: n=13), CMT grade I (CMT I: n=22), and CMT grade II/III (CMT: n=11). The patients underwent clinical and laboratory evaluation, mastectomy, clinical-pathological characterization of the tumor, morphology of the intratumoral inflammatory infiltrate, immunophenotyping of peripheral blood and tumors by flow cytometry, and assessment of VKINA by immunohistochemistry, in addition to survival analysis. The results indicated that the mesenchymal component associated with the myxoid matrix contributes to higher grading, nodal metastasis, and lower survival in MSC, IL12 possibly helps CMT I in tumor combat, the most aggressive tumors (grade II/III) presented greater infiltration of TCD4+ and TGF-β + , and expression of VKINA in the extracellular matrix. Thus, it is suggested that MSC has a characteristic microenvironment depending on its degree of aggressiveness. The mesenchymal component, the high expression of TGFβ+ , and VKINA influence tumor aggressiveness, while IL12 in CMT I helps in tumor combat. This is the first study to show the relationship between VKINA and IL12 and TGFβ+ in this histological subtype.