Zhao Wei-Li, Mourah Samia, Mounier Nicolas, Leboeuf Christophe, Daneshpouy Marjan Ertault, Legrès Luc, Meignin Veronique, Oksenhendler Eric, Maignin Christine Le, Calvo Fabien, Brière Josette, Gisselbrecht Christian, Janin Anne
ERM-0220, Institut Universitaire d'Hématologie, Université Paris VII, Paris, France.
Lab Invest. 2004 Nov;84(11):1512-9. doi: 10.1038/labinvest.3700145.
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.
血管内皮生长因子-A(VEGF-A)是内皮细胞增殖的主要刺激因子,在肿瘤血管生成中起重要作用。血管免疫母细胞性T细胞淋巴瘤(AITL)在淋巴瘤中显示出最显著的血管成分,其预后难以预测。为了评估VEGF-A在AITL中的临床意义,我们使用激光显微切割和定量聚合酶链反应研究了24例患者肿瘤淋巴结中VEGF-A基因的表达。VEGF-A基因在显微切割的淋巴瘤细胞和内皮细胞中均过度表达。淋巴瘤细胞中VEGF-A基因表达水平的升高,与内皮细胞一样,与结外受累和短生存时间相关。因此,在有淋巴瘤累及的淋巴结和骨髓中的这两种细胞类型中也发现了VEGF-A蛋白表达。淋巴结切片的三重免疫荧光标记显示,在淋巴瘤浸润区域的微血管内皮细胞上,VEGF-A蛋白及其受体VEGF-R1共表达。在这些区域,超微结构研究显示有营养不良性微血管。综上所述,VEGF-A基因表达作为AITL不良预后标志物的价值应予以考虑。除淋巴瘤细胞本身外,血管成分作为AITL的一个关键病理特征,也促进淋巴瘤的进展。