Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer.

Qiu-Wan Wu,Qing-Mo Yang,Zhi-Ming Zhang,Hong-Qiang She,Qiao-Lu Yang,Yu-Fan Huang,Jing Liang

doi:10.1186/1471-2407-12-47

Qiu-Wan Wu, Qing-Mo Yang + Show 5 more

Open Access

https://doi.org/10.1186/1471-2407-12-47

Copy DOI

Journal: BMC Cancer	Publication Date: Jan 27, 2012
Citations: 52	License type: cc-by

Affiliation: First Affiliated Hospital of Xiamen University

Abstract

BackgroundExtracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease.MethodsECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested.ResultsThe rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes (P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status (P < 0.05) and LMVD (P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining (P < 0.05).ConclusionsBoth ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer.

Highlights

Extracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, play important roles in the lymphatic dissemination of tumors
It has been reported that the basal epithelial cell layers of the epidermis and the myoepithelial cells of human breast tissue, prostate and salivary gland tissue can be stained by D2-40; but the morphology of these cells are distinct from the characteristic morphology of lymphatic endothelium [25,26]
We found that the tumor lymphatic vessel invasion (LVI) was established when at least one tumor cell cluster (“tumor emboli”) was clearly visible inside a D2-40 positive lymph vessel, according to criteria established by Hasebe et al [27]

Summary

Introduction

Extracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, play important roles in the lymphatic dissemination of tumors. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease. Recent studies have demonstrated that there is expansion of lymphatic networks within lymph nodes prior to the onset of metastasis [3]. The status of lymph node metastasis can be predicted by the presence of early lymphatic invasion. Increased numbers of lymphatic microvessels provide more opportunities for tumor cells to disseminate to the lymphatic system; LMVD has been shown to be correlated with lymphangiogenic factors, the presence of lymphatic metastasis and a poor prognosis in breast cancer [4]

Objectives

Methods

Results

Discussion

Conclusion