Localization of vascular endothelial growth factor and its receptors in digestive endocrine tumors: Correlation with microvessel density and clinicopathologic features
Localization of vascular endothelial growth factor and its receptors in digestive endocrine tumors: Correlation with microvessel density and clinicopathologic features
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DOI：
10.1053/hupa.2003.56
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Capella, C
中科院分区：
文献类型：
--
作者：
La Rosa, S;Uccella, S;Capella, C
血管生成是与肿瘤生长和恶性相关的过程，由几种生长因子刺激。其中之一是血管内皮生长因子（VEGF），其通过与2种特异性受体VEGFR 1和VEGFR 2结合而作用于内皮细胞。近年来的研究表明，VEGF的表达与微血管形成密切相关。肿瘤密度（MVD）和肿瘤进展。消化道内分泌肿瘤是一种异质性肿瘤，表现出可变的生物学侵袭性和行为，通常不能仅从形态学上预测。本研究旨在探讨VEGF、VEGFR 1和VEGFR 2在消化道内分泌肿瘤中的表达及其与MVD和恶性程度的关系。共84例标本的内分泌肿瘤和正常肠道和胰腺组织进行了免疫化学研究，使用特异性抗体针对VEGF，VEGFR 1，VEGFR 2，内皮抗原，胃肠胰腺激素。采用免疫细胞化学方法观察VEGF和VEGFRs的细胞定位。在正常组织中，VEGF免疫反应阳性表达于G细胞和PP细胞。超微结构上，VEGF定位于分泌颗粒内。正常内分泌细胞无VEGF表达。VEGF免疫反应阳性细胞在83例肿瘤中有40例，主要是G细胞和肠嗜铬细胞肿瘤。VEGFR 1-IR细胞在82个肿瘤中的44个中被发现，VEGFR 2-IR细胞在82个肿瘤中的55个中被发现，没有对任何特定肿瘤类型的偏好。VEGF及其受体的表达与MVD及恶性程度无关。这些结果表明，在正常组织中，内皮功能可能受到某些内分泌细胞产生的VECF的调节，并且VEGF/VEGFR结合机制可能参与肿瘤发生，但不参与肿瘤进展和侵袭性。
Angiogenesis, a process related to tumor growth and malignancy, is stimulated by several growth factors. Among these is vascular endothelial growth factor (VEGF), which acts on endothelial cells by binding with 2 specific receptors, VEGFR1 and VEGFR2. Recent studies have demonstrated that VEGF expression is correlated with microvessel. density (MVD) and tumor progression. Digestive endocrine tumors are heterogeneous neoplasms exhibiting variable biological aggressiveness and behavior that often are not predictable on morphologic grounds alone. The aims of this study were to evaluate the expression of VEGF, VEGFR1, and VEGFR2 in digestive endocrine tumors and to examine its correlation with MVD and malignancy. A total of 84 specimens from endocrine neoplasms and normal gut and pancreatic tissue were immunohistochemically studied using specific antibodies directed against VEGF, VEGFR1, VEGFR2, endothelial antigens, and gastroenteropancreatic hormones. Ultrastructural immunocytochemistry was performed to identify the cellular localization of VEGF and the VEGFRs. In normal tissues, VEGF immunoreactivity was detected in G cells and PP cells. Ultrastructurally, VEGF was localized within secretory granules. The VEGFRs were not significantly expressed by normal endocrine cells. VEGF-immunoreactive (IR) cells were detected in 40 of 83 tumors, mainly G cell and enterochromaffin cell neoplasms. VEGFR1-IR cells were found in 44 of 82 tumors, and VEGFR2-IR cells were found in 55 of 82 tumors, with no predilection for any specific tumor type. The expression of VEGF and its receptors did not correlate with MVD or malignancy. These results suggest that in normal tissues, endothelial functions may be regulated by VECF produced by some endocrine cells and that a VEGF/VEGFR binding mechanism may be involved in tumorigenesis, but not in tumor progression and aggressiveness.