散发性肾透明细胞癌组织中VHL基因突变、血管内皮生长因子表达及其与微血管形成的关系  

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：张宁[1] 龚侃[1] 果宏峰[1] 那熙 吴关 杨新宇[1] 辛殿旗[1] 那彦群[1] 

机构地区：[1]北京大学第一医院泌尿外科,北京大学泌尿外科研究所100034 [2]美国Rochester大学泌尿外科

出　　处：《中华医学杂志》2004年第19期1620-1624,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目 (3 0 3 5 0 0 0 7;3 0 10 0 184)

摘　　要：目的　探讨国人散发性肾透明细胞癌 (CCRCC)中vonHippel Lindau (VHL)基因突变、血管内皮生长因子 (VEGF)表达和微血管形成的关系和意义。方法　应用聚合酶链反应 (PCR)、PCR产物直接测序和免疫组化等方法分析 77例散发性肾透明细胞癌中VHL基因突变、VEGF和微血管密度(MVD)的情况。结果　VHL基因突变 4 0例 ( 5 1 9% ) ,VEGF染色阳性 6 1例 ( 79 2 % )。在VHL基因突变组中VEGF阳性率 ( 92 5 % )高于无突变组 ( 6 4 9% ) ,P =0 0 0 3;VHL基因突变组MVD均值 ( 76 0 80 /mm2 )也高于无突变组 ( 5 4 7 0 3/mm2 ) ,P =0 0 0 1。VEGF阳性组MVD均值 ( 715 95 /mm2 )高于VEGF阴性组 ( 4 37 4 4 /mm2 ) ,P =0 0 0 1。在VEGF阳性组中 ,按照VHL基因是否突变分组 ,突变组MVD值仍高于无突变组 ,P =0 0 11。结论　在国人散发性肾透明细胞癌中VHL基因突变率较高 ,其突变会使VEGF表达和MVD升高。VHL基因突变失活后除通过VEGF ,还可能通过其他机制促进肿瘤微血管的形成 ,并因此可能增加了CCRCC的恶性能力。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 microvasscularte 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/mm 2 and 715 95/mm 2 respectively, both significantly higher than those in the cases without VHL mutation and those without VEGF expression(547 03/mm 2 and 437 44/mm 2 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 mm 2, significantly higher than that of the cases with VEGF expression and without VHL mutation (547 03 mm 2, 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

关 键 词：VHL基因 突变 VEGF 肾透明细胞癌 散发性 MVD 血管内皮生长因子 结论 方法分析 情况 

分 类 号：R737.11[医药卫生—肿瘤]