Accelerated lymphangiogenesis in malignant lymphoma: Possible role of VEGF-A and VEGF-C

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.