Pathologic evaluation of tumor-associated macrophage density and vessel inflammation in invasive breast carcinomas (original) (raw)
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Journal of the Egyptian National Cancer Institute, 2020
Background Tumor-associated macrophages (TAMs) are important in regulating cross-talk between tumor cells and tumor microenvironment. TAMs are involved in multiple steps of tumor progression and invasion. This study aimed to compare CD163 expression with the widely used CD68 pan-macrophage marker in invasive breast carcinoma. Furthermore, it focused on assessing the significance of TAMs localization in relation to clinicopathological parameters. Results CD68 and CD163 immunohistochemical expressions within TAMs infiltrating both tumor nest (TN) and tumor stroma (TS) were evaluated in 60 specimens with invasive breast carcinoma. High CD68-positive stromal TAMs was significantly related to larger tumor, nodal metastasis and vascular invasion (p = 0.003, 0.037, 0.032, respectively), whereas high CD163-positive stromal TAMs was significantly related to larger tumors, nodal metastasis, stage III tumors, vascular invasion, estrogen receptor (ER) negativity, and triple-negative subtype (p ...
Breast cancer cell-derived cytokines, macrophages and cell adhesion: implications for metastasis
Anticancer research, 2011
Liver metastasis is associated with a proinflammatory microenvironment and up-regulation of cell adhesion molecules expressed by endothelial cells. The aim of this study was to characterize the interrelations between breast cancer cell-secreted cytokines, macrophages and E-selectin-mediated cancer cell adhesion and their role in metastasis of breast cancer. Three metastatic breast cancer cell lines (1590, KM22, ZE) were studied. Cell culture supernatants were screened for cytokines and the potential for cytokines to increase tumor-necrosis factor-α (TNF-α) production by ANA-1-macrophages was analyzed. E-Selectin-mediated tumor cell adhesion of fluorescence labelled tumor cells was evaluated by measurement of fluorescence intensity with and without E-selectin-blocking strategies (monoclonal antibodies, cimetidine). Tumor-specific cytokine secretion patterns were revealed. TNF-α secretion from cultured macrophages increased after incubation with tumor supernatants. Tumor cell adhesion...
Human pathology, 2017
Tumor associated macrophages (TAM) resemble M2 macrophages, promote tumor invasion and show strong expression of CD163 in breast cancer. We here investigated the association between CD163 positive macrophages and vascular invasion, molecular subgroups, mode of detection, and patient outcome. We performed a population-based, retrospective study of invasive breast cancer from the Norwegian Breast Cancer Screening Programme in Vestfold County (2004-2009), including 200 screen-detected and 82 interval cancers. Immunohistochemically CD163 positive macrophages were counted in the most active areas (hot-spots) and dichotomized as high (upper quartile) and low counts. Lymphatic vessel involvement (LVI) and blood vessel invasion (BVI) were recorded separately based on immunohistochemical staining (D2-40 and CD31 antibodies). High levels of CD163 positive macrophages were associated with blood vessel invasion and lymphatic involvement as well as interval cancer detection when compared to scre...
Annals of Surgical Oncology, 2012
Purpose. Macrophages play a major role in inflammatory processes and have been associated with poor prognosis in a variety of cancers, including breast cancer. Previously, we investigated the relationship of a subset of tumorassociated macrophages (PCNA ? TAMs) with clinicopathologic characteristics of breast cancer. We reported that high PCNA ? TAM counts were associated with hormone receptor (HR)-negative, high-grade tumors and early recurrence. To further understand the significance of elevated PCNA ? TAMs and the functionality of TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased in several cancer types. Methods. We performed immunohistochemistry using the Mac387 antibody on 367 invasive human breast cancer cases. Results were compared to previous PCNA ? TAM
Immunobiology, 2017
Breast cancer is the leading cause of cancer death in women worldwide with high morbidity and mortality. Tumor-associated macrophages (TAM) are major innate immune cells in the tumor microenvironment controlling primary tumor growth and metastasis. Neoadjuvant chemotherapy (NACT) is a conventional pre-operative treatment for breast cancer. In the present study we examined the distribution of TAM in five distinct intratumoral morphological compartments of human breast cancer and their correlation with clinical parameters after NACT. Our data indicated that CD68+ but not stabilin-1+ TAM in areas with parenchymal elements negatively correlate with lymphatic metastasis after NACT. However, in cases where lymphatic metastases were detected (28 out of 50 analyzed samples) both amount of CD68+ and stabilin-1+ macrophages in the areas with coarse fibrous stroma directly correlated with the number of positive lymph nodes. In patients with complete response to the preoperative NACT the average score of CD68 expression in the areas with coarse fibrous stroma was lower compared with cases of a partial response and stable disease. We concluded that function of TAM after NACT depends on their intratumoral localization and local tumor microenvironment which plays an important role in polarization of macrophages towards tumor-suppressive or tumor-supportive types.
Expert Review of …, 2011
While several inflammatory cell types participate in cancer development, macrophages specifically play a key role in breast cancer, where they appear to be part of the pathogenesis of high-grade tumors. Tumorassociated macrophages (TAMs) produce factors that promote angiogenesis, remodel tissue and dampen the immune response to tumors. Specific macrophage types contribute to increased metastases in animal models, while human studies show an association between TAMs and tumors with poor prognostic features. Macrophages display a spectrum of phenotypic states, with the tumor microenvironment skewing TAMs towards a 'nonclassical' activation state, known as the M2, or wound healing/regulatory state. These TAMs are found in high-risk breast cancers, making them an important therapeutic target to explore. Improved techniques for identifying TAMs should translate into clinical applications for prognosis and treatment.
Tumor-associated macrophages in breast cancer
Journal of mammary gland biology and neoplasia, 2002
Neoplastic cells form only one part of a complex network of cell types that make up a breast tumor. The normal cell types that make up the nonneoplastic components of tumors include fibroblasts, endothelium, and inflammatory cells, such as tumor associated macrophages (TAMs). TAMs have the potential to carry out both anti- and protumor activities In their antitumor role TAMs can present tumor antigens to cytotoxic T-cells and are capable of being directly cytotoxic to neoplastic cells. Conversely, TAMs are also able to promote tumor growth directly by secreting breast tumor mitogens, such as epidermal growth factor, and indirectly by stimulating tumor angiogenesis and metastasis. Recent studies have indicated that in breast cancers the protumor role of TAMs is dominant, and that TAMs may be executing a "wound healing" type of process in response to stimuli found in the tumor microenvironment, such as hypoxia. As such, TAMs may provide opportunities for future therapeutic i...
Tumor-associated macrophages: Oblivious confederates in invasive mammary carcinoma
Asian Journal of Oncology
Background: The infiltrating margins of carcinomas are associated with presence of inflammatory cell infiltrate which are an integral part of the tumor microenvironment. Amongst 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 aa association with the following pathological variables: tumor size, histological grade, nodal status, hormonal expression status and Her2Neu overexpression. Materials and Methods: 90 diagnosed archival cases of invasive mammary carcinomas at a tertiary care centre 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 TAMs (CD68 positive cells) was dichotomised into high (>50 CD68 positive cells/HPF) and low (<5050 CD68 positive cells/HPF) and compared with the above mentioned pathological variables using ...
Tumour-associated macrophages in breast cancer and their prognostic correlations
The Breast, 1998
S U M M A R Y. Breast cancer is known as a macrophage (Mps) infiltrated type of tumour. The biological and prognostic significance of this phenomenon is not clear. The intensity of intratumoural Mps infiltration as well as its correlation with reliable prognostic parameters has been studied. The extent of Mps infiltration was evaluated by immunohistochemistry in paraffin-embedded sections from formalin-fixed samples of 34 node-negative and 86 node-positive primary breast cancers using KP-1 (CD-68) DAK0 monoclonal antibody (MoAB) and polyclonal antibody to lysozyme. Intensive Mps infiltration was closely associated with absence of regional metastases: 16 (47%) node-negative and only 5 (5.8%) node-positive tumours were infiltrated intensively (more than 500 IQ-l+ cells in 40 high-power fields). However, when stratified into subgroups, intensity of Mps infiltration was strongly associated with prognostic parameters, which are traditionally considered to be the signs of bad prognosis (high tumour grade, oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and high mitotic rate).
Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma
Cancer research, 1996
Angiogenesis is a key process in tumor growth and metastasis and is a major independent prognostic factor in breast cancer. A range of cytokines stimulate the tumor neovasculature, and tumor-associated macrophages have been shown recently to produce several important angiogenic factors. We have quantified macrophage infiltration using Chalkley count morphometry in a series of invasive breast carcinomas to investigate the relationship between tumor-associated macrophage infiltration and tumor angiogenesis, and prognosis. There was a significant positive correlation between high vascular grade and increased macrophage index (P = 0.03), and a strong relationship was observed between increased macrophage counts and reduced relapse-free survival (P = 0.006) and reduced overall survival (P = 0.004) as an independent prognostic variable. These data indicate a role for macrophages in angiogenesis and prognosis in breast cancer and that this cell type may represent an important target for im...