散发性肾透明细胞癌VHL基因突变的研究

目的 了解散发性肾透明细胞癌组织中VHL（Von Hippel-landau）基因突变率及其临床意义。材料与方法 提取28例1998年4月-2000年1月间手术并获得病理诊断的散发性肾透明细胞癌及远离肿瘤的正常肾组织基因组DNA，采用单链构象多态性（SSCP）分析明确是否存在VHL基因有突变，分析VHL基因突变与肿瘤体积、分期、分级以及患者生存率等的关系。结果 远离肿瘤的正常肾组织中未检测到VHL基因的突变，10例（35．7％）癌组织标本中存在VHL基因的突变。VHL基因的突变率在T1a与T1b～T3间存在显著差异（P=0．035），肿瘤最大径4cm及以下者VHL基因突变率显著高于4cm以上者（P=0．011）。伴随VHL基因突变的患者5年生存率为100％，不伴随VHL基因突变者5年生存率为83％。结论 散发性肾透明细胞癌肿瘤组织中存在VHL基因突变，VHL基因突变较多发生于肿瘤的早期，VHL基因突变可能是肾透明细胞癌的有利预后因素。

The Mutation of Von Hippel - Lindau Gene in Sporadic Renal Clear Cell Carcinoma

Objective To evaluate somatic mutation of the von Hippel-Lindau (VHL) disease gene in tissue of sporadic clear cell renal cell carcinoma(CCRCC).Methods Total of 28 patients with CCRCC who underwent nephrectomy from April 1998 through January 2000 were examined for somatic VHL gene mutation by PCR-SSCP.Clinicopathologic and survival data were also collected.Statistical analyses were used to explore associations between the age of patients,tumor size,stage,grade,cyst,survival and VHL gene mutation respectively.Results VHL gene mutation was detected in 10(35.7%) CCRCC tumor samples.There was no mutation detected in all normal kidney tissues.The associations of VHL gene mutations with stage and tumor size were statistically significant.Those with age,grade,cyst were not statistically significant.The five year survival rate of patients with or without somatic VHL gene mutation was 100% and 83% respectively.The association of VHL gene mutations with five year survival rate of sporadic clear cell renal cell carcinoma was not statistically significant.Conclusions There were somatic mutations of VHL gene in tissues of sporadic clear cell renal cell carcinoma.The mutations were more frequently detected in early stage of CCRCC.The somatic VHL gene mutation maybe a beneficial prognostic factor of sporadic clear cell renal cell carcinoma.