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[散发性透明细胞肾细胞癌中冯·希佩尔-林道基因的突变及血管内皮生长因子的表达及其与血管生成的关系]

[Mutation of von Hippel-Lindau gene and expression of vascular endothelial growth factor in sporadic clear cell renal cell carcinoma and their relationships to angiogenesis].

作者信息

Zhang Ning, Gong Kan, Guo Hong-feng, Na Xi, Wu Guan, Yang Xin-yu, Xin Dian-qi, Na Yan-qun

机构信息

Department of Urology, the First Hospital of Peking University, Institute of Urology, Peking University, Beijing 100034, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2004 Oct 2;84(19):1620-4.

PMID:15569457
Abstract

OBJECTIVE

To evaluate the relationship between the mutation of the von Hippel-Lindau (VHL) gene and expression of vascular endothelial growth factor (VEGF) in sporadic clear cell renal cell carcinoma (CCRCC) and angiogenesis.

METHODS

Polymerase chain reaction (PCR) was used to detect the mutation of VHL gene in the specimens of cancerous tissue and normal tissues away from tumor from 77 patients with CCRCC. Immunohistochemistry was used to examine the expression of VEGF. CD34 staining was used to measure the microvascular density (MVD).

RESULTS

VHL gene mutations were detected in 40 cases (51.9%). The expression rate of VEGF was 79.2% (61 cases). The positive rate of VEGF in the cases with VHL mutation was 92.5%, significantly higher than that in the cases without VHL mutation (64.9%, P = 0.003). The levels of MVD was higher in the cases with VHL mutation and those with VEGF expression were 760.80/mm2 and 715.95/mm2 respectively, both significantly higher than those in the cases without VHL-mutation and those without VEGF expression (547.03/mm2 and 437.44/mm2 respectively, all P = 0.001). The cases with expression of VEGF were divided into two groups according the presence or absence of VHL gene mutations or not. The MVD of the cases with VEGF expression and VHL mutation was 760.80 mm2, significantly higher than that of the cases with VEGF expression and without VHL mutation (547.03 mm2, P = 0.011).

CONCLUSION

The mutation rate of VHL gene is high among the Chinese with sporadic CCRCC. VHL gene mutation increases significantly the VEGF expression, thus, and perhaps via other mechanism too, promoting the angiogenesis in tumor. The high level of MVD of the cases with VHL gene mutation may be related to the high malignant potential of CCRCC.

摘要

目的

评估散发性透明细胞肾细胞癌(CCRCC)中冯·希佩尔-林道(VHL)基因突变与血管内皮生长因子(VEGF)表达及血管生成之间的关系。

方法

采用聚合酶链反应(PCR)检测77例CCRCC患者癌组织及癌旁正常组织标本中VHL基因的突变情况。采用免疫组织化学法检测VEGF的表达。采用CD34染色法测量微血管密度(MVD)。

结果

40例(51.9%)检测到VHL基因突变。VEGF表达率为79.2%(61例)。VHL基因突变病例中VEGF阳性率为92.5%,显著高于无VHL基因突变病例(64.9%,P = 0.003)。VHL基因突变病例及VEGF表达病例的MVD水平较高,分别为760.80/mm²和715.95/mm²,均显著高于无VHL基因突变及无VEGF表达病例(分别为547.03/mm²和437.44/mm²,均P = 0.001)。根据是否存在VHL基因突变,将VEGF表达病例分为两组。VEGF表达且VHL基因突变病例的MVD为760.80 mm²,显著高于VEGF表达但无VHL基因突变病例(547.03 mm²,P = 0.011)。

结论

中国散发性CCRCC患者中VHL基因突变率较高。VHL基因突变显著增加VEGF表达,进而可能通过其他机制促进肿瘤血管生成。VHL基因突变病例的高MVD水平可能与CCRCC的高恶性潜能有关。

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