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

目的探讨国人散发性肾透明细胞癌(CCRCC)中von Hippd-Lndau(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40例(51．9％),VEGF染色阳性61例(79．2％)。在VHL基因突变组中VEGF阳性率(92．5％)高于无突变组(64．9％),P=0．003;VHL基因突变组MVD均值(760．80／mm^2)也高于无突变组(547．03／mm^2),P=0．001。VEGF阳性组MVD均值(715．95／mm^2)高于VEGF阴性组(437．44／mm^2),P=0．001。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=0．011。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。

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

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