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The aim of this study was to investigate the effect of vascular endothelialgrowth factor-C (VEGF-C) expression in tumor-associated macrophages (TAMs) onlymphatic microvessel density (LMVD) and lymphatic endothelial cell proliferation(LECP) and to determine the role of VEGF-C expression in lymphangiogenesis inpatients with breast cancer. Breast cancer tissue specimens confirmed by pathologicalanalysis were obtained from 75 patients. Samples were observed by microscopy analysisafter immunohistochemical double‑staining. The total number of TAMs and the numberof VEGF-C-positive TAMs were determined. LMVD and LECP were calculated for theintratumoral and peritumoral areas. Correlation analysis was performed among theseindexes, lymph vessel invasion (LVI) and lymph node metastasis in the peritumoralregions. Immunohistochemical double-staining demonstrated that VEGF-C was markedlyexpressed in TAMs. The number of TAMs, LMVD and LECP in the peritumoral areaswas significantly higher than that in the intratumoral areas (P&lt;0.001). Weobserved positive correlations between the following parameters: the number ofTAMs and the peritumoral LMVD (P&lt;0.001), the percentage of TAMs expressingVEGF-C and the peritumoral LMVD (P&lt;0.001), the number of TAMs and the peritumoralLECP (P&lt;0.001), and the percentage of TAMs expressing VEGF-C and the peritumoralLECP (P&lt;0.001). Furthermore, the total number of TAMs and VEGF-C-positive TAMs,LMVD and LECP in cases with lymph node metastasis or LVI were significantly highercompared to those in cases without lymph node metastasis or LVI (P&lt;0.01 orP&lt;0.05). Our findings suggest that TAMs play a critical role in tumor-inducedlymphangiogenesis through upregulating VEGF-C, which may contribute to lymphaticinvasion in breast cancer.

molecular medicine reports

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