肾细胞癌VHL基因改变与VEGF表达的关系及意义

目的：探讨肾细胞癌VHL基因异常与血管内皮生长因子（VEGF）表达的关系及意义。方法：应用聚合酶链反应（PCR）加单链构象多态性分析（SSCP）、多聚合酶链反应（Multiplex-PCR)及免疫组织化学方法检测42例肾细胞癌、18例远离肿瘤的正常肾脏及10例正常肾脏组织中VHL基因突变、异常甲基化及VEGF的表达。结果：肾癌组织中VHL基因改变（61．9％）与正常肾脏组织（3．6％）比较差别有显著性意义（P＜0．005），VHL基因失活与肾癌组织类型及临床分期相关，与病理分级无关。VEGF在肾癌组织（64．3％）与正常肾组织（21．4％）中的表达差别有显著性意义（P＜0．005），肾癌组织中VEGF表达与组织类型无关，与病理分级及临床分期相关，随病理分级及临床分期的升高而增高。VHL基因改变与VEGF表达间存在显著的相关性（P＜0．05）。结论：VHL基因在肾细胞癌中具有高频突变率，可负向调节VEGF的表达。

Abnormality of VHL gene and VEGF expression in primary renal cell carcinoma

Objective To evaluate the significance of t he abnormality of VHL gene and VEGF expression in primary renal cell carcinoma ( RCC). Methods Mutation and abnormal methylation of VHL g ene and the expression of VEGF were dtected by means of multiplex PCR,PCR-SSCP and immunohistochemistry in 42 cases of primary RCC,in 18 specimens adjacent to the neoplastic lesion and in 10 specimens of normal renal tissues. R esults The alteration rate of VHL gene was higher in RCC tissue (61. 9%) than in the normal renal tissue (3.6%,P<0.005) and correlated with the p athological type and stage of the tumor but not with the grade.The positive r ate of VEGF was higher in RCC tissue (64.29%) than in normal renal tissue (21.4 %,P<0.005) and correlated with the grade and stage of the tumor but not wit h the pathological type of RCC.The higher the grade and stage of the tumor the h igher would be the positive rate of VEGF expression which correlated significant ly with the abnormality of VHL gene. Conclusions VHL gen e abnormality may play a significant role in the tumorigenesis of RCC and can de regulate the expression of VEGF in primary RCC.It might play an important role i n the tumorigenesis and progression of RCC.