Tumor-Associated Macrophages: Oblivious Confederates in Invasive Mammary Carcinoma

Abstract

The infiltrating margins of carcinomas are associated with the presence of inflammatory cell infiltrate which are an integral part of the tumor microenvironment. Among the inflammatory cells, tumor-associated macrophages (TAMs) play a key role in the tumorigenesis. This study elucidates the density of TAMs in invasive mammary carcinomas and attempts to establish an association with the following pathological variables: tumor size, histological grade, nodal status, hormonal expression status and Her2Neu overexpression. Ninety diagnosed archival cases of invasive mammary carcinomas at a tertiary care center were included. Density of TAMs was assessed by using CD68 which is a pan-macrophage marker by immunohistochemistry on the archival tissue blocks. The density of TAMs (CD68 positive cells) was dichotomized into high (> 50 CD68 positive cells/HPF) and low (< 50 CD68 positive cells/HPF) and compared with the above-mentioned pathological variables using appropriate statistical tests. The density of TAMs was significantly higher around the infiltrating edge of the carcinoma in comparison with the adjoining normal terminal duct lobular units. The density of TAMs was more in the infiltrating edge of the tumor than within the tumor nodule/nests. A higher TAM density showed a significant association in tumors having large tumor size, higher histological grade, nodal metastasis, the absence of ER and PR expression and Her2Neu overexpression (p value < 0.05). TAMs play an important role in tumor progression in invasive mammary carcinomas. This is as a result of the multiple roles enacted by TAMs in the various stages of tumor development starting from tumor growth, invasion, angiogenesis and metastases. Targeted therapy against TAMs has great potential in being important components of future treatment strategies against breast carcinomas.