The effect of vascular endothelial growth factor C expression in tumor-associated macrophages on lymphangiogenesis and lymphatic metastasis in breast cancer

Ding, Mingxing; Fu, Xiaoyan; Tan, Haidong; Wang, Ruiquan; Chen, Zhimei; Ding, Shiping

doi:10.3892/mmr.2012.1043

Cited by 45 publications

(44 citation statements)

References 28 publications

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“…The details of the included studies are exhibited in Table 110111213141516171819202122. The publication years ranged from 2005 to 2014.…”

Section: Resultsmentioning

confidence: 99%

Intratumoral and peritumoral lymphatic vessel density both correlate with lymph node metastasis in breast cancer

Zhang

et al. 2017

Sci Rep

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The status of lymph node involvement is an important prognostic factor for breast cancer. However, the presence of intratumoral lymphatic vessels in primary tumor lesions and the relationship between lymphatic vessel density (LVD) and lymph node metastasis (LNM) have not been firmly established. Therefore, we performed a meta-analysis study to investigate these issues. According to the pre-established inclusion and exclusion criteria, 13 studies, involving 1029 breast cancer patients, were included in this study. Using immunohistochemical staining, intratumoral lymphatic vessels were detected in 40.07% of breast cancer patients (240/599), and peritumoral lymphatics were detected in 77.09% (397/515). All studies demonstrated that peritumoral LVD was higher than intratumoral LVD, with a pooled standard mean difference and 95% confidence interval (95% CI) of 1.75 (1.28 to 2.21). Both intratumoral LVD and peritumoral LVD positively correlated with LNM, with correlation coefficients of 0.14 (95% CI 0.05 to 0.23) and 0.31 (95% CI 0.13 to 0.49), respectively. In summary, our study reports the overall detection rate of intratumoral lymphatics and demonstrates the associations between intratumoral LVD, peritumoral LVD, and LNM in breast cancer. Additionally, controlled studies with a larger number of subjects are needed to establish these relationships.

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“…The details of the included studies are exhibited in Table 110111213141516171819202122. The publication years ranged from 2005 to 2014.…”

Section: Resultsmentioning

confidence: 99%

Intratumoral and peritumoral lymphatic vessel density both correlate with lymph node metastasis in breast cancer

Zhang

et al. 2017

Sci Rep

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“…According to the detection area of lymphatic vessels, the included 12 studies were divided into three subgroups as follows: total LVD (without distinguishing peritumoral and intratumoral) ( n = 7) [11, 17, 24, 25, 27, 29, 31], peritumoral LVD ( n = 5) [16, 18, 22, 36, 38], and intratumoral LVD ( n = 3) [18, 22, 38]. The main outcomes are summarized in Figure 2.…”

Section: Resultsmentioning

confidence: 99%

The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis

Zhang

et al. 2016

Oncotarget

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Lymph node status is one of the key parameters used for determining the stage of breast cancer progression. The relationship of lymphatic vessel density (LVD), lymphovascular invasion (LVI), and lymph node metastasis (LNM) has not been clearly demonstrated yet. Databases of PubMed, Embase, and Web of Science were searched from inception up to 25 May 2016. Spearman correlation coefficient (r) and 95% confidence interval (CI) were used to determine the relationship within each group. Based on pre-established inclusion criteria, 28 studies involving 2920 breast cancer patients were included in this study. The r values of LVD-LVI, LVD-LNM, and LVI-LNM were 0.45 (95% CI: 0.31 to 0.57), 0.32 (95% CI: 0.23 to 0.40), and 0.24 (95% CI: 0.19 to 0.28), respectively. Compared with intratumoral LVD, peritumoral LVD showed more robust correlation with LVI (r = 0.53, 95% CI: 0.27 to 0.72) and LNM (r = 0.33, 95% CI: 0.18 to 0.46). The patients in LNM positive group presented with higher LVI detection rate of 45.85%, while in LNM negative group with detection rate of 23.85%. The results describe a triangle relationship between LVD, LVI, and LNM in breast cancer. Both LVD and LVI are indicated to be valuable predictors of LNM occurrence. Compared with intratumoral lymphatic vessels, peritumoral lymphatics might be the main disseminate route for breast tumor cells.

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“…For example, positive correlation between overall density of CD68+ TAM and lymph node (LN) metastases was found in human papillary thyroid carcinoma, endometrial cancer, cervical cancer, pulmonary adenocarcinoma, gastric cancer, breast cancer and others (Ding et al, 2012;Ohno et al, 2004;Qing et al, 2012;Riabov et al, 2014;Schoppmann et al, 2002;Takanami et al, 1999;Wu et al, 2012). Detrimental role of TAM in lymphatic metastases was mainly associated with their ability to produce pro-lymphangiogenic factors VEGF-C and VEGF-D that induce growth of intratumoral lymphatic vessels (Riabov et al, 2014;Iwata et al, 2007;Schoppmann et al, 2006;Song et al, 2013;Yang et al, 2011).…”

Section: Introductionmentioning

confidence: 95%

CD68+, but not stabilin-1+ tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer

et al. 2017

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Tumor associated macrophages (TAM) support tumor growth and metastasis in several animal models of breast cancer, and TAM amount is predictive for efficient tumor growth and metastatic spread via blood circulation. However, limited information is available about intratumoral TAM heterogeneity and functional role of TAM subpopulations in tumor progression. The aim of our study was to examine correlation of TAM presence in various morphological segments of human breast cancer with clinical parameters. Thirty six female patients with nonspecific invasive breast cancer T1-4N0-3M0 were included in the study. Morphological examination was performed using Carl Zeiss Axio Lab.A1 and MiraxMidiZeiss. Immunohistochemical and immunofluorescence/confocal microcopy analysis was used to detect CD68 and stabilin-1 in 5 different tumor segments: (1) areas with soft fibrous stroma; (2) areas with coarse fibrous stroma; (3) areas of maximum stromal-and-parenchymal relationship; (4) parenchymal elements; (5) gaps of ductal tumor structures. The highest expression of CD68 was in areas with soft fibrous stroma or areas of maximum stromal-and-parenchymal relationship (79%). The lowest expression of CD68 was in areas with coarse fiber stroma (23%). Inverse correlation of tumor size and expression of CD68 in gaps of tubular tumor structures was found (R=-0.67; p=0.02). In case of the lymph node metastases the average score of CD68 expression in ductal gaps tumor structures was lower (1.4±0.5) compared to negative lymph nodes case (3.1±1.0; F=10.9; p=0.007). Confocal microscopy identified 3 phenotypes of TAM: CD68/stabilin-1; CD68/stabilin-1 (over 50%); and CD68/stabilin-1. However, expression of stabilin-1 did not correlate with lymph node metastasis. We concluded, that increased amount of CD68+TAM in gaps of ductal tumor structures is protective against metastatic spread in regional lymph nodes.

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The effect of vascular endothelial growth factor C expression in tumor-associated macrophages on lymphangiogenesis and lymphatic metastasis in breast cancer

Cited by 45 publications

References 28 publications

Intratumoral and peritumoral lymphatic vessel density both correlate with lymph node metastasis in breast cancer

Intratumoral and peritumoral lymphatic vessel density both correlate with lymph node metastasis in breast cancer

The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis

CD68+, but not stabilin-1+ tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer

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