Expression patterns of hypoxic markers at the invasive margin of colorectal cancers and liver metastases
Expression patterns of hypoxic markers at the invasive margin of colorectal cancers and liver metastases
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DOI：
10.1016/j.ejso.2009.05.008
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发表时间：
2009-12-01
期刊：
影响因子：
3.8
通讯作者：
Jayne, D. G.
中科院分区：
文献类型：
--
作者：
Rajaganeshan, R.;Prasad, R.;Jayne, D. G.
目的：探讨缺氧在大肠癌原发灶及肝转移灶发生发展中的作用。要看协会缺氧与更积极的phenotypes.Methods：档案组织检索从55例患者和组织微阵列构建使用组织从边缘和中心的肿瘤。缺氧标志物Hif-1 α、VEGF、CA-9、VRL和Glut-1使用免疫组织化学检测可视化，并使用数字化图像的半定量分析进行定量。通过病例笔记审查检索临床详细信息和结局数据，并与统计数据库中的缺氧标志物数据进行比较。结果：与肿瘤中心相比，在原发性结直肠癌（CRC）和肝转移中，所有标志物的表达均显着增加。推切缘结直肠癌与VEGF表达增加相关。在原发性CRC中观察到Hif-1 α与VEGF（p < 0.001）、Hif-1 α与VHL（p < 0.001）之间的正相关性，但未观察到Hif-1 α与Glut-1或CA-9之间的相关性。一个显着的趋势，更糟糕的无病生存率也注意到与增加的边缘表达HIF-1 α（p < 0.001）和VHL（p = 0.02）在原发性CRC，但没有为任何其他marker.Conclusion：这项研究强调了在大肠癌生物学浸润性边缘的重要性。它是对缺氧影响最敏感的区域，其对上调HIF-1 α能力的依赖性对无病生存有显著影响。(C)2009爱思唯尔有限公司版权所有。
Aim: To understand the role of hypoxia in cancer progression of primary colorectal cancer and colorectal liver metastases. To look at associations of hypoxia with more aggressive phenotypes.Methods: Archival tissue was retrieved from 55 patients and tissue micro arrays were constructed using tissue from the margin and the Centre of the tumour. Hypoxia markers Hif-1 alpha, Vegf, CA-9, VRL and Glut-1 were visualised using immunohistochemical detection and quantified using semi-quantitative analysis of the digitised images. Clinical details and outcome data were retrieved by case note review and collated with hypoxia markers data in a statistical database.Results: Significantly increased expression of all markers were found at the tumour margin compared to the tumour Centre, both in primary colorectal cancer (CRC) and liver metastases. Pushing margin CRC was associated with increased Vegf expression. Positive correlations were observed between Hif-1 alpha and Vegf (p < 0.001), and Hif-1 alpha and VHL (p < 0.001) in primary CRC, but no relationship was seen between Hif-1 alpha and either Glut-1 or CA-9. A significant trend to worse disease-free survival was also noted with increased margin expression of Hif-1 alpha (p < 0.001) and VHL (p = 0.02) in primary CRC, but not for any of the other markers.Conclusion: This study underlines the importance of the invasive margin in colorectal cancer biology. It is the area most responsive to hypoxic influences and its dependence on its ability to up-regulate Hif-1 alpha has a significant impact on disease-free survival. (C) 2009 Elsevier Ltd. All rights reserved.