Abstract
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.
Highlights
Cancer metastasis is the leading cause of mortality in patients diagnosed with breast cancer and other malignant tumors [1]
It is known that tumor angiogenesis and its indicator blood vessel denstiy are closely associated with the clinicopathological outcomes in breast cancer [7]
Our study shows that high peritumoral lymphatic vessel density (LVD) strongly correlates with lymphovascular invasion (LVI) (r = 0.53, 95% confidence interval (CI): 0.27 to 0.72), while high intratumoral LVD moderately correlates with LVI (r = 0.33, 95% confidence interval (95% CI): 0.18 to 0.46)
Summary
Cancer metastasis is the leading cause of mortality in patients diagnosed with breast cancer and other malignant tumors [1]. Lymph node status is commonly used to identify a patient’s prognosis, tumor stage, and treatment modality [2]. The progress of lymphatic metastasis is thought to involve the proliferation of lymphatic vessels (lymphangiogenesis), lymphovascular invasion, and LNM step by step [1]. The mechanism leading to tumor cells spread via lymphatic vessels (lymphovascular invasion, LVI) to the regional and distant lymph nodes has not been clearly demonstrated [4]. During the last two decades, substantial progress within the field has rapidly lead to the recognition of the lymphatic system as an active player involved in lots of malignant tumors [5]. The clinical role of lymphangiogenesis and www.impactjournals.com/oncotarget its indicator lymph vessel density (LVD) is needed to be further investigated [8, 9]
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