Vascular Endothelial Growth Factor-A is Expressed Both on Lymphoma Cells and Endothelial Cells in Angioimmunoblastic T-cell Lymphoma and Related to Lymphoma Progression

Vascular endothelial growth factor-A (VEGF-A), a main stimulator of endothelial cell proliferation, plays an important role on tumor angiogenesis. Angioimmunoblastic T-cell lymphoma (AITL) show the most prominent vascular component among lymphomas and their prognosis is difficult to predict. To assess the clinical significance of VEGF-A in AITL, VEGF-A gene expression was studied in the tumoral lymph nodes of 24 patients using laser microdissection and quantitative polymerase chain reaction. VEGF-A gene was overexpressed in both microdissected lymphoma and endothelial cells. Increased levels of VEGF-A gene expression in lymphoma cells, as in endothelial cells, were related to extranodal involvement and to short survival time. Accordingly, VEGF-A protein expression was also found in both types of cells in lymph nodes and bone marrows with lymphomatous involvement. Triple immunofluorescent labeling on lymph node sections showed that VEGF-A protein and its receptor VEGF-R1 were coexpressed on endothelial cells of microvessels in the areas of lymphoma invasion. In these areas, ultrastructural study showed dystrophic microvessels. Taken together, the value of VEGF-A gene expression as an adverse prognostic marker in AITL should thus be considered. In addition to lymphoma cells themselves, the vascular component, a critical pathologic characteristic in AITL, also contributes to lymphoma progression.