von Hipple-Lindau基因突变与散发性肾透明细胞癌患者预后的关系

目的 探讨von Hippel-Lindau(VHL)抑癌基因突变与散发性肾透明细胞癌患者预后的关系. 方法应用聚合酶链反应(PCR)、PCR产物直接测序分析74例散发性肾透明细胞癌组织标本和相应远离肿瘤的正常组织标本中VHL基因突变情况.74例患者,病理分期为T1 51例(68.9%),T2 9例(12.2%),T3 14例(18.9%);病理分级为G1 15例(20.3%),G2 50例(67.6%),G39例(12.2%).随访其预后并进行统计学分析. 结果 VHL基因突变者40例(54.1%),不同病理分期和分级的肿瘤中VHL基因突变率差异无统计学意义(P值分别为0.915和0.237).随访34~107个月.平均71个月,因肿瘤死亡7例,出现远处肿瘤转移11例,5年无瘤生存率为78%.VHL基因突变组肿瘤死亡或转移等阳性事件发生率(15.0%,6/40)明显低于非突变组(35.3%,12/34,P=0.043).Logistic回归分析表明.患者预后与肿瘤病理分期、分级呈正相关,而与VHL基因是否突变呈负相关,三者的P值分别为0.016、0.024和0.033.对于T3和G3肿瘤患者,VHL基因突变者预后更好.P值分别为0.010和0.048. 结论 散发性肾透明细胞癌患者中VHL基因突变广泛,肾癌的病理分期和分级仍然是评估患者预后的有效指标.VHL基因突变失活可能提示肾透明细胞癌患者预后更好,尤其对于高分期和高分级肿瘤患者.

Relationship between von Hipple-Lindau tumor suppressor gene mutations and the prognosis of Chinese sporadic clear cell renal cell carcinoma

Objective To evaluate the relationship between von Hippel-Lindau (VHL) gene mutations and the prognosis of Chinese sporadic clear cell renal cell carcinoma (CCRCC). Methods VHL gene mutations were detected by polymerase chain reaction (PCR), direct DNA sequencing in 74 paired specimens of sporadic CCRCC and normal kidney. The mutation findings, pathologic fea-tures and prognostic characteristics were analyzed. Results Fifty-one patients (68.9%) were in clinical stage T1, 9 patients (12.2%) were in T2 and 14 patients (18.9%) were in T3. In the aspect of pathological grade, 15 patients (20.3%) were in G1, 50 patients (67.6%) were in G2 and 9 pa-tients (12.2%) were in G3. VHL gene mutations were detected in 40 of 74 cases (54.1%). There were no significant differences of VHL gene mutations in different pathological grade and clinical stage of CCRCC, P=0.915, P=0.237, respectively. All patients were followed up for 34 to 107 months (mean 71 months). Seven patients died of CCRCC. Another 11 patients developed CCRCC related me-tastasis. Five-year tumor-free survival was 78%. The incidence of death or metastasis of CCRCC in VHL gene mutation group (15.0%, 6/40) was significant lower than non-mutation group (35.3%,12/34), P=0.043. Logistic regression results showed that lower tumor pathological grade and stage, better patients' prognosis would be (P=0.016, P=0.024, respectively). However, VHL gene muta-tion was related with better prognosis (P=0.033). This association was stronger among patients with high grade tumors (G3, P=0.048). Conclusions There are frequent VHL gene mutations in spo-radic Chinese CCRCC. Tumors' pathological grade and clinical stage are the important parameters for prognosis. However, VHL mutations are strongly associated with better cancer specific survival for CCRCC patients. These associations are relatively stronger in patients with high grade tumors.