In human invasive breast ductal carcinoma, tumor stromal macrophages and tumor nest macrophages have distinct relationships with clinicopathological parameters and tumor angiogenesis

Abstract

Tumor-associated macrophages play a crucial role in breast cancer progression and tumor angiogenesis. However, evaluation of tumor-associated macrophages incorporating their histological locations is lacking. The aim of this study was to clarify whether macrophages in tumor stroma and macrophages in tumor cell nests have distinctive properties in relation to pertinent breast cancer clinicopathological parameters and tumor angiogenesis. In 94 human invasive breast ductal carcinomas, tumor-associated macrophages were immunostained with anti-CD68 antibody and counted or graded according to these histological locations. Microvessels were immunostained with anti-CD34 antibody and counted for microvessel density. We found that the presence of tumor stromal and tumor nest macrophages was closely correlated (p = 0.001). Both tumor stromal and tumor nest macrophages were associated with mitotic count (p = 0.001 and p = 0.037, respectively). However, only higher tumor stromal macrophage grades were associated with higher tumor grades (p = 0.004) and negative estrogen receptor status (p = 0.007). Multivariate analysis showed that tumors with a high mitotic count score (score 3 vs. scores 1 and 2) had a higher tumor stromal macrophage density (Grades III and IV) when adjusted for tumor size, tubule formation, and estrogen receptor status (odds ratio 3.41, p = 0.010). The tumor nest macrophage count significantly correlated with the microvessel density (p < 0.001). These results imply that tumor stromal macrophages and tumor nest macrophages residing in different tumor microenvironments have distinctive roles.

A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages

“…While TAM density in primary breast cancer has been correlated with poor prognosis 26–28 , a CSC-niche involving TAMs has not been demonstrated microscopically in patient tumor tissues. We undertook to verify direct contact between TAMs and CD90 hi CSCs in patient breast cancer tissue by immunofluorescence analyses with anti-CD90 and -CD68 (a cell-surface protein expressed largely by macrophages) antibodies.…”

Spontaneous Mesotheliomas in F344/N Rats Are Characterized by Dysregulation of Cellular Growth and Immune Function Pathways

“…2012), pro-survival signaling through the AKT/PIK3 pathway (Yunta and Lazo 2003), or are expressed by tumor cells and TAMs in a variety of human cancers (Maniecki et al . 2012; Shabo and Svanvik 2011;Ch’ng et al . 2013; Feng et al .…”

Role of tumor‐associated macrophages in human malignancies: friend or foe?

“…The density of CD68 + TAMs in the tumor stroma, but not in the tumor nest, was an independent prognostic factor for reduced survival of patients with breast cancer. 35 Another report 36 indicated that high CD68 + TAM counts in the tumor stroma, but not in the tumor nest, were associated with higher tumor grades and negative estrogen receptor status, whereas those in the tumor nest were significantly correlated with microvessel density. The authors suggested that tumor stromal macrophages and tumor nest macrophages residing in different microenvironments have distinct roles.…”

“…34 Stromal TAMs linked to poor prognosis more closely than were intratumoral TAMs. 35,36 Lung cancer…”