Estudo das subpopulações M1 e M2 de macrófagos associados ao tumor (MAT) nos carcinomas mamários de cadelas: associação com parâmetros clínicopatológicos e sobrevida

Abstract

Macrophages represent a major component of leukocyte populations within neoplasms and are characterized as important for tumor behavior in several human cancers. However, little information regarding its role in canine mammary tumors (CMT) is available. Accordingly, the aim of this study was to address the potential role of tumor-associated macrophages (TAM) in CMT. For that, 82 female dogs had their tumors excised and clinically, histologically, and immunohistochemically evaluated, subsequently classifying tumors as with low or high macrophage counts. They were also categorized as intraepithelial (iTAM), stromal (sTAM), and total (tTAM) TAM. Higher macrophage count was associated with clinical stage and vascular invasion for all TAM categories, while tumor size were also associated with higher tTAM, as well as lymph node metastasis was associated with high sTAM and tTAM counts. Additionally, there was association with higher counts and an invasive tumor profile instead of an in situ carcinomatous pattern. A higher tTAM count was associated with tumor type, high proliferative rates, and vascular microdensity, as well as with a worse prognosis based on survival analysis. Tissue laser confocal microscopy revealed that almost all macrophages infiltrating malignant tumors with high TAM counts expressed CD206 while all benign tumors showed macrophages expressing NOS2, indicating a phenotypic shift from M1 toward M2 macrophage subpopulations in malignant tumors. Additionally, a triple staining pattern revealed a mixed M1/M2 profile in some tumors, characterizing an intermediate state. The results indicate that TAM are related with mammary cancer invasiveness and metastatic potential in dogs.