Association of Macrophage Infiltration with Angiogenesis and Prognosis in Invasive Breast Carcinoma1 (original) (raw)
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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...
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).
British journal of cancer, 1999
Necrosis is a common feature of invasive carcinoma of the breast and is caused by chronic ischaemia leading to infarction. Although necrosis was previously assumed to be due to a generally poor blood supply in the tumour, in this study we show that it is present in tumours with focal areas of high vascular density situated away from the actual sites of necrosis. This may account, in part, for the previous observation that necrosis is linked to poor prognosis in this disease. Highly angiogenic tumours often display blood vessel shunting from one tumour area to another, which further exacerbates ischaemia and the formation of tumour necrosis. We have recently demonstrated that high focal microphage infiltration into breast tumours is significantly associated with increased tumour angiogenesis and poor prognosis and that the macrophages accumulate in poorly vascularized, hypoxic areas within breast tumours. In order to investigate the interactions of macrophages with chronic ischaemia ...
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...
Journal of Cancer Research and Clinical Oncology, 2005
Purpose and method: Monocyte chemotactic protein-1 (MCP-1) is a chemokine involved in the macrophage infiltration of tumor tissue. Tumor-associated macrophages (TAMs) are a population of mononuclear phagocytic cells that can have a complex function in tumor biology. The aim of this study was to determine the possible correlation between parenchymal MCP-1 expression and TAM level by immunohistochemical analysis of 97 invasive ductal breast carcinomas, not otherwise specified (NOS), and to investigate their relation with tumor size, histological grade, mitotic activity index (MAI) and lymph node status. Secondly, the MCP-1 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in eight samples of normal breast tissue and 27 samples of invasive breast carcinomas and compared with TAMs. Results: MCP-1 immunoreactivity was present in tumor cells (17/97), but also in TAMs, fibroblasts and endothelial cells. The statistical analysis did not show a significant correlation between MCP-1 expression in tumoral epithelium and tumor size, histological grade, MAI, lymph node status or TAMs. The results of RT-PCR showed that, in all cases of breast carcinomas (27/ 27) and the majority of normal breast tissues (7/8), the number of detected MCP-1 cDNA copies was above the detection limit. However, carcinomas showed higher levels of MCP-1 mRNA than normal breast tissue. Nevertheless, the statistical analysis did not find a significant correlation between MCP-1 expression and macrophage infiltrations. Conclusion: These results indicate that MCP-1 is probably not the only and/or crucial factor involved in macrophage attraction to tumor locus in breast carcinoma.
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 ...
Oncology Letters, 2017
Tumor-associated macrophages (TAMs) are major constituents of the tumor microenvironment in solid tumors and have been implicated as mediators of tumor progression, invasion and metastasis. Correspondingly, accumulation of TAMs is associated with unfavorable clinical outcomes in numerous types of solid tumors. E-selectin is a hallmark of inflammation and a key adhesion molecule that accommodates the initial contact of circulating immune cells with the inflamed vessel surface. Currently, the association between E-selectin and TAMs is not fully elucidated; therefore, the present study investigated the association between vessel inflammation, TAM infiltration, and clinical outcome in breast cancer. A total of 53 procedure-naïve invasive breast cancer cases were immunohistochemically analyzed for the presence of cluster of differentiation (CD)68 + TAMs, E-selectin + vessels and tumor inflammation. The association between CD68 and E-selectin expression, and tumor inflammation as well as overall survival was evaluated using Kaplan-Meier survival curves and multivariable Cox's proportional hazards regression analysis. The abundance of TAMs was identified to be positively associated with tumor inflammation, estrogen receptor and E-selectin expression levels. A greater prevalence of TAMs and tumor inflammation was significantly associated with shorter overall survival times. E-selectin expression levels were significantly higher in tumor vessels among elderly patients, but were not associated with overall survival. The abundance of TAMs was associated with the presence of E-selectin-expressing inflamed tumor vessels and tumor inflammation, as well as overall survival in patients with invasive breast carcinoma.
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.
Macrophages Regulate the Angiogenic Switch in a Mouse Model of Breast Cancer
The development of a tumor vasculature or access to the host vasculature is a crucial step for the survival and metastasis of malignant tumors. Although therapeutic strategies attempting to inhibit this step during tumor development are being developed, the biological regulation of this process is still largely unknown. Using a transgenic mouse susceptible to mammary cancer, PyMT mice, we have characterized the development of the vasculature in mammary tumors during their progression to malignancy. We show that the onset of the angiogenic switch, identified as the formation of a high-density vessel network, is closely associated with the transition to malignancy. More importantly, both the angiogenic switch and the progression to malignancy are regulated by infiltrated macrophages in the primary mammary tumors. Inhibition of the macrophage infiltration into the tumor delayed the angiogenic switch and malignant transition whereas genetic restoration of the macrophage population specifically in these tumors rescued the vessel phenotype. Furthermore, premature induction of macrophage infiltration into premalignant lesions promoted an early onset of the angiogenic switch independent of tumor progression. Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy. (Cancer Res 2006; 66(23): 11238-46)