Expression of vascular endothelial growth factor (VEGF) and its receptors (VEGF-R1 (Flt-1) and VEGF-R2 (KDR/Flk-1)) in tumorlets and in neuroendocrine cell hyperplasia of the lung

Expression of vascular endothelial growth factor (VEGF) and its receptors (VEGF-R1 (Flt-1) and VEGF-R2 (KDR/Flk-1)) in tumorlets and in neuroendocrine cell hyperplasia of the lung
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DOI:
10.1016/j.humpath.2004.07.009
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发表时间:
2004-10-01
期刊:
影响因子:
3.3
通讯作者:
Brambilla, E
Brambilla, E
中科院分区:
医学3区
文献类型:
--
作者:
Sartelet, H;Decaussin, M;Brambilla, E

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肺小瘤和神经内分泌 (NE) 细胞增生是 NE 细胞增生连续谱的一部分,从 NE 增生到类癌。血管内皮生长因子(VEGF)是一种有效的内皮细胞有丝分裂原,已被证明在缺氧肺中会增加。我们假设在这种情况下经常发生的小肿瘤和 NE 细胞增生是 VEGF 分泌的部分原因。对 12 个含有肿瘤和 NE 细胞增生的肺组织的石蜡切片进行 VEGF 以及 VEGF-RI 和 VEGF-R2 的免疫组织化学分析,并与 11 个肺标本的对照组平行。比较两组支气管上皮细胞和内皮细胞中VEGF及其受体的表达量。 VEGF 及其受体在小肿瘤和 NE 细胞增生中一致表达。与对照组肺相比,带有肿瘤的肺内皮细胞中的 VEGF 染色评分显着较高,但支气管上皮细胞中没有差异。支气管上皮细胞(P = 0.001)和内皮细胞(P = 0.006)上VEGF-R1表达显着增加,内皮细胞上VEGF-R2表达显着增加(P = 0.044)。对照组和肺荷瘤组中VEGF和VFGF-R1表达水平均呈显着正相关(P=0.04),而VEGF与VEGF-R2表达水平之间无显着相关性(P=0.1)。我们得出的结论是,VEGF 在局部 NE 细胞增殖中高表达,无恶性潜力,可能参与局部纤维化的发展。 (C) 2004 Elsevier Inc. 保留所有权利。
Pulmonary tumorlets and neuroendocrine (NE) cell hyperplasia are part of a continuous spectrum of NE-cell hyperplasia, going from NE hyperplasia to carcinoid. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that has been shown to be increased in hypoxic lung. We hypothesized that tumorlets and NE-cell hyperplasia, which occur frequently in this context, were partly responsible for VEGF secretion. Immunohistochemical analysis of VEGF and both VEGF-RI and VEGF-R2 was performed on paraffin sections of 12 lung tissues containing tumorlets and NE-cell hyperplasia in parallel with a control group of 11 lung specimens. VEGF and its receptor expressions were compared in bronchial epithelial cells and endothelial cells in both groups. VEGF and its receptors were consistently expressed in tumorlets and in NE-cell hyperplasia. When compared with control group lungs, the staining score for VEGF in lung bearing tumorlets was significantly higher in endothelial cells, but was not different in bronchial epithelial cells. VEGF-R1 expression was significantly increased both on bronchial epithelial cells (P = 0.001) and endothelial cells (P = 0.006), and VEGF-R2 expression was significantly increased on endothelial cell (P = 0.044). There was a significant positive correlation between the level of expression of VEGF and VFGF-R1 (P = 0.04) in both control groups and lung bearing tumorlets, but there was no significant correlation between VEGF and VEGF-R2 expression (P = 0.1). We concluded that VEGF is highly expressed in localized NE cell proliferations without potential of malignancy and might participate in local development of fibrosis. (C) 2004 Elsevier Inc. All rights reserved.