The relationship of erythropoietin overexpression with von Hippel-Lindau tumour suppressor gene mutations between hypoxia-inducible factor-1α and-2α in sporadic clear cell renal carcinoma
The relationship of erythropoietin overexpression with von Hippel-Lindau tumour suppressor gene mutations between hypoxia-inducible factor-1α and-2α in sporadic clear cell renal carcinoma
复制标题
DOI：
10.3892/ijmm_00000541
复制
发表时间：
2010-12-01
影响因子：
5.4
通讯作者：
Na, Yanqun
中科院分区：
文献类型：
--
作者：
Gong, Kan;Zhang, Ning;Na, Yanqun
von Hippel-Lindau（VHL）肿瘤抑制蛋白水平的降低与缺氧诱导因子（HIF）的上调相关，导致肿瘤增殖、血管生成和进展增加。促红细胞生成素（EPO）是HIF的靶基因，其在散发性透明细胞肾细胞癌（sCCRCC）中的作用尚不清楚。在这项研究中，我们测定了82例肾切除术后确诊为sCCRCC患者的EPO表达水平及其与VHL突变和HIF-1 α和HIF-2 α表达的相关性。我们鉴定VHL基因的改变，采用多重聚合酶链反应，纯化聚合酶链反应产物，并直接测序。对肿瘤和相应的正常组织进行HIF-1 α、HIF-2 α和EPO的免疫组织化学染色。数据进行了分析方面的临床病理因素。EPO在sCCRCC肿瘤中的检出率为87.8%，而正常组织中的检出率为7.3%。EPO表达与VHL基因异常的肿瘤相关。在VHL基因表达异常的标本中，EPO阳性率为95.6%，而VHL基因表达正常的标本中EPO阳性率为78.3%（P
Decreased levels of von Hippel-Lindau (VHL) tumour suppressor protein are associated with up-regulation of hypoxia-inducible factor (HIF), leading to increased tumour proliferation, angiogenesis and progression. The role of erythropoietin (EPO), a target gene for HIF, remains unknown for sporadic clear cell renal cell carcinoma (sCCRCC). In this study, we determined expression levels of EPO, and its correlation with VHL mutations and HIF-1 alpha and HIF-2 alpha expression in 82 patients identified with sCCRCC following nephrectomy. We identified VHL gene alterations using multiplex polymerase chain reaction, purifying products of polymerase chain reaction, and direct sequencing. Immunohistochemical staining for HIF-1 alpha, HIF-2 alpha and EPO was performed for tumour and corresponding normal tissues. Data were analyzed with respect to clinicopathological factors. EPO was detected in 87.8% of sCCRCC tumours versus 7.3% for normal tissues. EPO expression was related to tumours demonstrating VHL gene abnormalities. Of specimens with VHL alterations 95.6% tested positive for EPO, versus 78.3% when VHL gene expression was normal (P