Accelerated lymphangiogenesis in malignant lymphoma: possible role of VEGF‐A and VEGF‐C

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Abstract
There is little information regarding the lymphangiogenesis of malignant lymphoma. In this study, we evaluated the lymphangiogenesis and angiogenesis in 44 lymph nodes of 39 malignant lymphomas and five non-reactive normal lymph nodes, based on the lymphatic vessel density (LVD) and microvessel density (MVD) calculated by the computer-assisted assessment of vessel density. The LVD of malignant lymphomas was significantly higher than that of non-reactive normal lymph nodes, irrespective of subtypes (P = 0.00077). On the contrary, there was no difference in MVD between malignant lymphomas and non-reactive normal lymph nodes, except for diffuse large B cell lymphomas, which had a significantly low value of MVD, in comparison with non-reactive normal lymph nodes (P = 0.009). We further examined the expression of vascular endothelial growth factor (VEGF)-C and VEGF-A, which function on lymphangiogenesis in lymph node samples. VEGF-C was expressed in 36 of 39 malignant lymphomas. All 39 of the malignant lymphoma samples expressed VEGF-A. Furthermore, the level of LVD and VEGF-A or VEGF-C was positively correlated. These findings suggest that lymphangiogenesis is actively developed in lymph nodes of malignant lymphomas and it may be induced by both VEGF-A and VEGF-C secreted from lymphoma cells.