Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival

Abstract

Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-beta staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer

“…It has previously been shown that macrophage traits, manifested as CD163 expression, in breast and rectal cancer cells are related to early distant recurrence and reduced patient survival [52,27]. These observations are substantiated in the present study.…”

“…Lymphatic and blood vessels are examined by using mouse monoclonal D2-40 antibody (Abcam, Cambridge, UK) and mouse monoclonal anti-CD31 antibody (Dako, Denmark), respectively. These antibodies are well characterized and have been used in many previous studies [27,[34][35][36][37][38][39]. Serial sections of 5 μm were cut from formalin-fixed paraffin-embedded tissue blocks, deparaffinized in xylene and hydrated in a series of graded alcohols (100 %, 95 %, and 70 %).…”

“…Serial sections of 5 μm were cut from formalin-fixed paraffin-embedded tissue blocks, deparaffinized in xylene and hydrated in a series of graded alcohols (100 %, 95 %, and 70 %). The sections were stained with CD163, CD31 and D2-40 antibodies according to methods used in our previous studies [27,40,41,28].…”

“…CD163 is expressed in M2 macrophages [3]. Recent studies report that about 50 % of patients with breast cancer and 23 % with rectal cancer exhibit phenotypic macrophage traits by expressing CD163 antigen, which is associated with early distant recurrence and poor survival [27,28]. It is suggested that macrophage traits in cancer cells might be explained by fusion between cancer cells and macrophages [29][30][31][32][33].…”

Overexpression of Semaphorin4D Indicates Poor Prognosis and Prompts Monocyte Differentiation toward M2 Macrophages in Epithelial Ovarian Cancer

“…CD163, more specific than CD68 marker, is expressed in the M2 macrophages. Several studies had already proved that high M2 macrophage count indicated tumor more aggressive and poor prognosis, including breast cancer (Shabo et al, 2008), lung adenocarcinoma (Zhang et al, 2011), and classical Hodgkin's lymphoma (Sanchez-Espiridion et al, 2012). Moreover, Lan et al recently showed that the infiltration of CD163-positive M2 macrophages as well as activation of macrophages towards the M2 phenotype may contribute to poor survival in advanced ovarian cancer (Lan et al, 2013), which was consistent with our results that demonstrated that both high M2 macrophage count in primary tumor and percent in ascites were closely related to EOC patients with advanced stage and platinum resistant and refractory and suggested a shorter OS and PFS.…”