Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray
Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray
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DOI：
10.1002/cncr.21783
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发表时间：
2006-04-15
期刊：
影响因子：
6.2
通讯作者：
Burtness, BA
中科院分区：
文献类型：
--
作者：
Chung, GG;Yoon, HH;Burtness, BA
背景。血管内皮生长因子（VEGF）在胰腺癌中的表达通常是定性或半定量的。本研究的目的是使用一系列称为AQUA的算法来定量评估组织微阵列（tma）上的蛋白表达，以比较VEGF及其主要受体VEGF受体1 （FLT-1）和VEGF受体1 （FLK-1）在胰腺癌tma上的原位表达。tma是通过排列从耶鲁大学病理学系档案中获得的76例胰腺腺癌样本（1996-2002）的1.5 mm核心来构建的。AQUA的染色与标准免疫组织化学类似，涉及抗原检索和一抗的应用，但有荧光检测。载玻片用4′，6-二氨基-2-苯基吲哚反染色进行核显示，用细胞角蛋白反染色进行膜显示。使用的一抗是VEGF、FLT-1、FLK-1和细胞角化蛋白。正如预期的那样，疾病分期是预后的重要指标。评估肿瘤膜内VEGF及其受体的总量，并将其分为四分位数。Kaplan-Meier生存曲线显示VEGF和FLK-1与预后无明显相关性。然而，FLT-1的表达有显著相关性，FLT-1表达水平最低的肿瘤患者生存率最差（P = 0.0038）。在多变量分析中，FLT-1表达是总生存的独立预后因素（P = 0.0044）。VEGF及其2种主要受体在胰腺肿瘤中均有不同程度的表达。FLT-1的低表达与不良预后和晚期之间存在显著关联，提示肿瘤中这种VEGF受体的表达是疾病侵袭性较低的标志。
BACKGROUND. Measures of vascular endothelial growth factor (VEGF) expression in pancreatic cancer typically have been qualitative or semiquantitative. The objective of this study was to use a series of algorithms called AQUA that quantitatively assesses protein expression on tissue microarrays (TMAs) to compare in situ expression of VEGF and its primary receptors, VEGF receptor 1 (FLT-1) and VEGF receptor 1 (FLK-1), on a pancreatic cancer TMA.METHODS. TMAs were constructed by arraying 1.5-mm cores from 76 samples of pancreatic adenocarcinoma (1996-2002) that were obtained from the archives of the Yale Department of Pathology. The staining for AQUA was similar to standard immunohistochemistry and involved antigen retrieval and the application of primary antibodies, but with epifluorescence detection. Slides were counterstained with 4',6-diamidino-2-phenylindole for nuclear visualization and cytokeratin for membrane visualization. The primary antibodies Used were VEGF, FLT-1, FLK-1, and cytokeratin.RESULTS. Disease stage was highly prognostic for outcome, as expected. Total amounts of VEGF and its receptors were assessed within the tumor mask and were divided into quartiles. Kaplan-Meier survival curves showed that VEGF and FLK-1 were not associated clearly with outcome. However, the expression of FLT-1 was correlated significantly, and the patients who had tumors with the lowest expression FLT-1 levels had the worst survival (P = .0038). In multivariate analysis, FLT-1 expression was an independent prognostic factor for overall survival (P = .0044).CONCLUSIONS. VEGF and its 2 principal receptors were expressed to varying degrees in tumors of the pancreas. A significant association was found between low expression of FLT-1 and both poor prognosis and advanced stage, suggesting that tumor expression of this VEGF receptor is a marker of less aggressive disease.