Caracterização da resposta inflamatória nos carcinomas mamários em cadelas

Abstract

Two different experiments were conducted using female do with mammary carcinoma, in order to characterize the inflammatory response associated with cancer and perform immunophenotyping of leukocytes in peripheral blood by flow cytometry. In the first experiment we were studied 51 breast tumors, histologically classified into two groups: carcinoma in mixed tumors (MC-BMT=31) and carcinomas (MC=20), which were submitted to morphometric analysis of inflammatory cells and clinical-pathological systematic, and was determining the survival rate of dogs. From these parameters, we found that the MC group was associated with advanced clinical stage, high histological grade and lung metastasis. The inflammation was more diffuse and intense in the MC group, when compared to MC-BMT, lymphocytes being the predominant cell type. Multivariate analysis showed only lymphocytic infiltrate intensity 600 (P = 0.02) was an independent prognostic factor. Further 24 animals were selected (MC-BMT = 16 and MC=8) to determine the subtypes of infiltrating lymphocytes in the tumor. The percentage of T cells was higher in group MC-BMT, without metastasis, while the percentage of B lymphocytes was higher in animals with metastases MC-BMT (P <0.05). The relative percentage of CD4+ T lymphocytes was significantly higher in animals with metastases (both MC-BMT and MC) (P <0.05), while the proportion of CD8+ cells was higher in MC-BMT without metastasis. Whatever type of tumor, the animals with a high proportion of CD4+ T cells and low CD8+ T cells showed a lower survival rate. Apparently, the subtype of lymphocyte, the amount and timing of initiation of the inflammatory response induced by cytokines, are factors that define the inflammatory process will act as a promoter or inhibitor of tumor development. In the second experiment were evaluated 49 bitches (MC-BMT=29 and MC=20) to determine the profile of leukocytes in peripheral blood and observed that the CD4+ T cells are associated with tumor progression, while the CD8+ T cells inhibit tumor development. From this analysis, we proposed two parameters, CD4+ / CD8+ ratio for the group MC-BMT and IMF in monocytes for the MC group, which showed significant clinical and prognostic value, allowing the segregation of dogs with a high probability of survival or death, respectively. These results may help better understanding of the immunologic heterogeneity of canine mammary carcinomas, providing alternative tools to establish possible therapeutic protocols based on the immunophenotypic profile of these tumors.