Loss of tumor-associated macrophages and vascular endothelial growth factor immunoexpression in solid mammary carcinoma in dogs

Abstract

Tumor-associated macrophages (TAM) are related to poor prognosis in canine mammary tumors (CMT). An association between TAM and sustained angiogenesis has been implicated with malignancy; however, comparison of the expression of TAM and vascular endothelial growth factor (VEGF) in different histologic types of CMT has not been completely studied. The objective of this study was to evaluate the immunostaining of TAM and VEGF in four different types of malignant CMT. Ninety-nine mammary carcinomas [tubular (29), tubulopapillary (22), mixed-type (28) and solid carcinoma (20)] were evaluated by immunohistochemical staining using MAC387 and VG-1 to detect TAM and VEGF immunoexpression, respectively. The total number of positive macrophages within the tumor was used for TAM immunolabeling and a score of four categories was used for VEGF immunolabeling. TAM immunoexpression was found to be statistically higher in tubular carcinomas than in solid carcinomas (P=0.0015). Differences between other types of carcinoma were not statistically significant. VEGF score was higher in tubular, papillary and mixed-type carcinomas than in solid carcinomas (P<0.0001). A positive relationship between the highest mean value of TAM and VEGF immunoexpression was also found (P=0.0015). TAM and VEGF expressions can be lost in more aggressive CMT, as in solid carcinoma. Furthermore, regardless of histologic type, higher numbers of TAM are associated with higher scores of VEGF, thus favoring the relationship between TAM and angiogenesis.