Gong Kan, Zhang Ning, Na Xi, Wu Guan, Yang Xin-yu, Xin Dian-qi, Na Yan-qun
Department of Urology, The First Hospital of Peking University, Institute of Urology, Peking University, Beijing 100034, China.
Zhonghua Wai Ke Za Zhi. 2005 Mar 15;43(6):390-3.
To evaluate the expression of hypoxia inducible factor (HIF)-1alpha, 2alpha in sporadic clear cell renal cell carcinoma and their relationships to the mutations of von Hippel-Lindau (VHL) gene.
Mutations of VHL gene, expression of HIF-1alpha and 2alpha were detected by polymerase chain reaction (PCR), direct DNA sequencing and immunohistochemistry in 77 cases of Chinese sporadic clear cell renal cell carcinoma (CCRCC). The stage was pT(1)N(0)M(0)in 55 patients (71%), pT(2)N(0)M(0) in 7 patients (9%), pT(3)N(0)M(0) in 14 patients (18%), and pT(4)N(0)M(0) in 1 patient (1%). The classification according to the tumor nuclear grading system showed 15 carcinomas (19%) of tumor nuclear grade 1, 56 (73%) of tumor nuclear grade 2 and 6 (8%) of tumor nuclear grade 3.
None of the VHL gene mutations were found in all the normal tissue specimens. VHL gene mutations were detected in 40 (52%) cases of CCRCC. The positive rate of HIF-2alpha (81%) was higher than that of HIF-1alpha (66%) (chi(2) = 23.310, P < 0.01); The positive rate of HIF-1alpha and HIF-2alpha in the cases of mutations (98% and 93% respectively) was higher than that of them in non-mutations (32% and 68% respectively) (chi(2) = 36.386, 7.617, P < 0.01); The correlation between HIF-1alpha and VHL gene mutations was closer than that between HIF-2alpha and VHL gene mutations (partial correlation coefficiency was 4.481 and 2.027 respectively, P < 0.01). The expression of HIF-1alpha and 2alpha in different pathological grade and stage of CCRCC showed no significant difference (P > 0.05).
Our study suggests that VHL gene mutations are frequent in sporadic CCRCC, and the high expression of HIF-1alpha and 2alpha are found in the group of VHL mutations. However, we have not found significant correlation between the expression of HIF-1alpha and 2alpha and pathological grade and stage of CCRCC in our study.
评估缺氧诱导因子（HIF）-1α、2α在散发性透明细胞肾细胞癌中的表达及其与冯·希佩尔-林道（VHL）基因突变的关系。
采用聚合酶链反应（PCR）、直接DNA测序和免疫组织化学方法检测77例中国散发性透明细胞肾细胞癌（CCRCC）患者的VHL基因突变、HIF-1α和2α表达。55例患者（71%）分期为pT(1)N(0)M(0)，7例（9%）为pT(2)N(0)M(0)，14例（18%）为pT(3)N(0)M(0)，1例（1%）为pT(4)N(0)M(0)。根据肿瘤核分级系统分类显示，肿瘤核1级癌15例（19%），肿瘤核2级56例（73%），肿瘤核3级6例（8%）。
所有正常组织标本均未发现VHL基因突变。40例（52%）CCRCC患者检测到VHL基因突变。HIF-2α阳性率（81%）高于HIF-1α（66%）（χ² = 23.310，P < 0.01）；突变病例中HIF-1α和HIF-2α阳性率分别为98%和93%，高于非突变病例（分别为32%和68%）（χ² = 36.386、7.617，P < 0.01）；HIF-1α与VHL基因突变的相关性比HIF-2α与VHL基因突变的相关性更密切（偏相关系数分别为4.481和2.027，P < 0.01）。CCRCC不同病理分级和分期中HIF-1α和2α的表达无显著差异（P > 0.05）。
我们的研究表明，散发性CCRCC中VHL基因突变常见，VHL突变组中HIF-1α和2α高表达。然而，在我们的研究中未发现HIF-1α和2α表达与CCRCC病理分级和分期之间存在显著相关性。
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