Lord Reginald V N, Park Ji Min, Wickramasinghe Kumari, DeMeester Steven R, Oberg Stefan, Salonga Dennis, Singer Jon, Peters Jeffrey H, Danenberg Kathleen D, Demeester Tom R, Danenberg Peter V
Department of Surgery and Cardiothoracic Surgery, University of Southern California Keck School of Medicine, Los Angeles, USA.
J Thorac Cardiovasc Surg. 2003 Feb;125(2):246-53. doi: 10.1067/mtc.2003.203.
This study was undertaken to investigate the role of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in the development and progression of Barrett esophagus and adenocarcinomas of the esophagus and gastroesophageal junction.
Vascular endothelial growth factor and basic fibroblast growth factor messenger RNA expression levels, relative to the control gene encoding beta-actin, were measured by using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector system) in specimens of Barrett intestinal metaplasia (n = 16), dysplasia (n = 11), adenocarcinoma (n = l 5), and matching normal squamous esophageal tissues (n = 35). Vascular endothelial growth factor and basic fibroblast growth factor protein expression and CD31(+) microvessel density were assessed by means of immunohistochemistry in 25 tissue sections that included representative areas for each of these Barrett stages.
Expression levels were significantly increased in adenocarcinoma compared with in either normal squamous mucosa (P <.0001 for both genes) or intestinal metaplasia (vascular endothelial growth factor, P =.002; basic fibroblast growth factor, P <.0001). Vascular endothelial growth factor levels were also significantly higher in cancer tissues compared with dysplasia tissues (P =.024, Mann-Whitney U test). Basic fibroblast growth factor expression was also significantly increased in Barrett dysplastic mucosa compared with in intestinal metaplasia or normal esophageal mucosa. Microvessel density was generally higher in adenocarcinoma compared with in preneoplastic Barrett tissues. The pattern of vascular endothelial growth factor and basic fibroblast growth factor protein expression was similar to the messenger RNA expression pattern, with the exception that mucin-containing goblet cells stained intensely for vascular endothelial growth factor and only weak vascular endothelial growth factor staining was present in some adenocarcinomas.
Vascular endothelial growth factor and basic fibroblast growth factor messenger RNA expression levels are significantly upregulated in esophageal and gastroesophageal junction adenocarcinomas, suggesting a role for these angiogenic factors in the development of these cancers. Vascular endothelial growth factor and basic fibroblast growth factor messenger RNA expression levels are also increased in some Barrett esophagus tissues, with this increase occurring at an earlier stage for basic fibroblast growth factor than for vascular endothelial growth factor. Basic fibroblast growth factor protein expression pattern is similar to the messenger RNA expression pattern, but unlike the messenger RNA findings, vascular endothelial growth factor protein expression is strongest in goblet cells.
本研究旨在探讨血管生成因子血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）在巴雷特食管、食管腺癌及胃食管交界腺癌的发生发展过程中的作用。
采用定量逆转录-聚合酶链反应法（ABI 7700序列检测系统），以编码β-肌动蛋白的对照基因作为参照，检测巴雷特肠化生标本（n = 16）、发育异常标本（n = 11）、腺癌标本（n = 15）以及配对的正常食管鳞状组织标本（n = 35）中VEGF和bFGF信使核糖核酸（mRNA）的表达水平。通过免疫组织化学方法，在25个组织切片中评估VEGF和bFGF蛋白表达以及CD31(+)微血管密度，这些组织切片包含巴雷特各阶段的代表性区域。
与正常鳞状黏膜相比，腺癌中的表达水平显著升高（两个基因的P均<0.0001），与肠化生相比也显著升高（VEGF，P = 0.002；bFGF，P < 0.0001）。癌组织中的VEGF水平与发育异常组织相比也显著更高（P = 0.024，曼-惠特尼U检验）。与肠化生或正常食管黏膜相比，巴雷特发育异常黏膜中的bFGF表达也显著增加。腺癌中的微血管密度通常比癌前巴雷特组织中的更高。VEGF和bFGF蛋白表达模式与mRNA表达模式相似，不同之处在于含黏液的杯状细胞VEGF染色强烈，而在一些腺癌中VEGF染色较弱。
食管及胃食管交界腺癌中VEGF和bFGF信使核糖核酸表达水平显著上调，提示这些血管生成因子在这些癌症的发生发展中起作用。在一些巴雷特食管组织中VEGF和bFGF信使核糖核酸表达水平也升高，且bFGF的升高比VEGF出现得更早。bFGF蛋白表达模式与信使核糖核酸表达模式相似，但与信使核糖核酸结果不同的是，VEGF蛋白在杯状细胞中表达最强。
