Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy
Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy
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DOI：
10.1038/labinvest.3700697
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发表时间：
2008-01-01
影响因子：
5
通讯作者：
Natkunam, Yasodha
中科院分区：
文献类型：
--
作者：
Gratzinger, Dita;Zhao, Shuchun;Natkunam, Yasodha
血管内皮生长因子介导的信号传导在弥漫性大B细胞淋巴瘤中至少具有两种潜在作用：增强血管生成，以及增强自分泌血管内皮生长因子受体介导的信号传导诱导的淋巴瘤细胞增殖和/或存活。我们最近发现，表达高水平血管内皮生长因子蛋白的弥漫性大B细胞淋巴瘤也表达高水平的血管内皮生长因子受体1和血管内皮生长因子受体2。我们现在已经评估了一个更大的多机构队列的原发弥漫性大B细胞淋巴瘤患者治疗蒽环类药物为基础的治疗，以解决是否肿瘤血管，或表达血管内皮生长因子蛋白及其受体，有助于患者的结果。我们的研究结果表明，增加肿瘤血管与不良的总生存率（P=0.047），是独立的国际预后指数。相比之下，淋巴瘤细胞血管内皮生长因子受体-1的高表达与总生存率的改善相关（P=0.044）。淋巴瘤细胞高血管内皮生长因子和血管内皮生长因子受体-1蛋白表达的组合确定了一个亚组患者的总体（P=0.003）和无进展生存期（P=0.026）改善，这些结果也是独立的国际预后指数。这种配体-受体对过度表达的预后意义表明，通过血管内皮生长因子受体-1的自分泌信号可能代表了弥漫性大B细胞淋巴瘤的生存或增殖途径。对自分泌血管内皮生长因子受体1介导的信号传导的依赖可能使一部分弥漫性大B细胞淋巴瘤对蒽环类药物治疗敏感
Vascular endothelial growth factor-mediated signaling has at least two potential roles in diffuse large B cell lymphoma: potentiation of angiogenesis, and potentiation of lymphoma cell proliferation and/or survival induced by autocrine vascular endothelial growth factor receptor-mediated signaling. We have recently shown that diffuse large B cell lymphomas expressing high levels of vascular endothelial growth factor protein also express high levels of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2. We have now assessed a larger multi-institutional cohort of patients with de novo diffuse large B cell lymphoma treated with anthracycline-based therapy to address whether tumor vascularity, or expression of vascular endothelial growth factor protein and its receptors, contribute to patient outcomes. Our results show that increased tumor vascularity is associated with poor overall survival (P=0.047), and is independent of the international prognostic index. High expression of vascular endothelial growth factor receptor-1 by lymphoma cells by contrast is associated with improved overall survival (P=0.044). The combination of high vascular endothelial growth factor and vascular endothelial growth factor receptor-1 protein expression by lymphoma cells identifies a subgroup of patients with improved overall (P=0.003) and progression-free (P=0.026) survival; these findings are also independent of the international prognostic index. The prognostic significance of overexpression of this ligand-receptor pair suggests that autocrine signaling via vascular endothelial growth factor receptor-1 may represent a survival or proliferation pathway in diffuse large B cell lymphoma. Dependence on autocrine vascular endothelial growth factor receptor-1-mediated signaling may render a subset of diffuse large B-cell lymphomas susceptible to anthracycline-based therapy.