期刊
BRITISH JOURNAL OF CANCER
卷 108, 期 2, 页码 429-437出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.538
关键词
Phaeochromocytoma; paraganglioma; carbonic anhydrase IX; Hif-1 alpha; VEGF; mTOR
类别
资金
- MRC
- BBSRC
- NIHR
- Integrative Mammalian Biology (IMB) Capacity Building Award
- EuroCHIP grant [FP7-HEALTH-2009-241592]
- NIHR Imperial Biomedical Research Centre within the Academic Health Sciences Centre
- Wellcome Trust McMichael Clinical Research Facility
Background: There are no reliable markers of malignancy in phaeochromocytomas (PCC) and paragangliomas (PGL). We investigated the relevance of the mammalian target of rapamycin (mTOR)/AKT and hypoxic pathways as novel immunohistochemical markers of malignancy. Methods: Tissue microarray blocks were constructed with a total of 100 tumours (10 metastatic) and 20 normal adrenomedullary samples. Sections were immunostained for hypoxia-inducible factor 1 alpha (Hif-1 alpha), vascular endothelial growth factor A (VEGF-A), mTOR, carbonic anhydrase IX (CaIX) and AKT. The predictive performance of these markers was studied using univariate, multivariate and receiver operating characteristic analyses. Results: In all, 100 consecutive patients, 64% PCC, 29% familial with a median tumour size of 4.7 cm (range 1-14) were included. Univariate analyses showed Hif-1 alpha overexpression, tumour necrosis, size 45 cm, capsular and vascular invasion to be predictors of metastasis. In multivariate analysis, Hif-1 alpha, necrosis and vascular invasion remained as independent predictors of metastasis. Hif-1 alpha was the most discriminatory biomarker for the presence of metastatic diffusion. Strong membranous CaIX expression was seen in von Hippel-Lindau (VHL) PCC as opposed to other subtypes. Conclusion: Lack of vascular invasion, tumour necrosis and low Hif-1 alpha expression identify tumours with lower risk of malignancy. We propose membranous CaIX expression as a potential marker for VHL disease in patients presenting with PCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据