Microvessel density and expression of vascular endothelial growth factor and its receptors in diffuse large B-cell lymphoma subtypes
Microvessel density and expression of vascular endothelial growth factor and its receptors in diffuse large B-cell lymphoma subtypes
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DOI：
10.2353/ajpath.2007.060901
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发表时间：
2007-04-01
影响因子：
6
通讯作者：
Natkunam, Yasodha
中科院分区：
文献类型：
--
作者：
Gratzinger, Dita;Zhao, Shuchun;Natkunam, Yasodha
血管生成在包括血淋巴瘤在内的肿瘤中起主要作用。我们利用组织芯片的免疫组化评估，评估了弥漫性大b细胞淋巴瘤临床和生物学相关亚型中血管生成与血管内皮生长因子及其受体表达之间的关系。我们发现弥漫性大b细胞淋巴瘤标本显示较高的局部血管内皮生长因子表达，相应地微血管也较高。密度，暗示淋巴瘤细胞诱导局部肿瘤血管生成。此外，在生长因子受体表达较高的标本中，局部血管内皮生长因子表达较高，提示存在自分泌促生长反馈回路。弥漫性大b细胞淋巴瘤的生发中心样亚型和非生发中心样亚型在生物学和预后上是不同的。有趣的是，只有更具临床侵袭性的非生殖中心样亚型中有微血管。血管内皮生长因子表达较高的标本密度显著增高；血管内皮生长因子受体-1的高表达与血管内皮生长因子的高表达也是如此。这些差异可能对两种弥漫性大b细胞淋巴瘤亚型对抗血管内皮生长因子和抗血管生成治疗的反应性具有重要意义。
Angiogenesis is known to play a major role in neoplasia, including hematolymphoid neoplasia. We assessed the relationships among angiogenesis and expression of vascular endothelial growth factor and its receptors in the context of clinically and biologically relevant subtypes of diffuse large B-cell lymphoma using immunohistochemical evaluation of tissue microarrays. We found that diffuse large B-cell lymphoma specimens showing higher local vascular endothelial growth factor expression showed correspondingly higher microvessel. density, implying that lymphoma cells induce local tumor angiogenesis. in addition, local vascular endothelial growth factor expression was higher in those specimens showing higher expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. The germinal center-like and nongerminal center-like subtypes of diffuse large B-cell lymphoma were biologically and prognostically distinct. Interestingly, only in the more clinically aggressive nongerminal center-like subtype were microvessel. densities significantly higher in specimens showing higher vascular endothelial growth factor expression; the same was true for the finding of higher vascular endothelial growth factor receptor-1 expression in conjunction with higher vascular endothelial growth factor expression. These differences may have important implications for the responsiveness of the two diffuse large B-cell lymphoma subtypes to anti-vascular endothelial growth factor and anti-angiogenic therapies.