缺氧诱导因子和血管内皮生长因子在非遗传性肾透明细胞癌中的表达及意义  

Expression of hypoxia-inducible factor-1-α, hypoxia-inducible factor-2α and vascular endothelial growth factor in sporadic clear cell renal cell carcinoma and their significance in the pathogenesis thereof

作　　者：张宁[1] 龚侃[1] 杨新宇[1] 辛殿旗[1] 那彦群[1] 

机构地区：[1]北京大学第一医院泌尿外科,北京大学泌尿外科研究所

出　　处：《中华医学杂志》2006年第22期1526-1529,共4页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30350007;30100184)

摘　　要：目的探讨缺氧诱导因子-1α(HIF-1α)、HIF-2α、血管内皮生长因子(VEGF)和微血管密度(MVD)在肾透明细胞癌中的表达情况,分析四者的关系及意义。方法应用免疫组化方法分析107例肾透明细胞癌中HIF-1α、HIF-2α、VEGF和MVD的表达情况。结果本组HIF-2α的阳性染色率(80·5%)明显高于HIF-1α(69·2%)(P<0·01)。HIF-1α和HIF-2α阳性组中VEGF的阳性率(90·5%和89·8%)明显高于它们阴性组的VEGF阳性率(51·5%和26·3%),P<0·01。HIF-2α和VEGF的表达与MVD存在正相关关系,(Spearman相关系数分别为0·500和0·513),P<0·01。但肿瘤的病理分级和分期与HIF-1α、2α的表达无相关性,P>0·05。结论HIF-2α在肾透明细胞癌中的表达比HIF-1α更广泛,两者与VEGF的表达正相关。HIF-2α对VEGF的正向调控和促血管生成作用都明显强于HIF-1α。未发现两者的表达与肿瘤病理分级和分期的相关性。Objective To investigate the expression of hypoxia-indncible factor （HIF）-1-α, HIF- 2α, and vascular endothelial growth factor （VEGF） in sporadic clear cell renal cell carcinoma （CCRCC） and to analyze the relationship among them. Methods Samples of CCRCC were obtained from 107 patients during resection. Immunohistochemistry was used to detect the expression of HIF-1-α, HIF-2α, and VEGF in the tumor tissues and normal kidney tissues distant from the tumor. The microvessel density （MVD） was observed by microscopy. Results HIF-1-α and HIF-2α were not expressed in the normal kidney tissues. However, in the tumor tissues the HIF-1-α positive rate was 69. 2% （74/107）, significantly lower than that of the HIF-2-α （80. 5%, 88/107, P = 0. 001 ）, the VEGF positive rate was 78.5% （84/107）. The VEGF positive rate of the HIF-1-α-positive group was 90. 5%, significantly higher than that of the HIF-1-α- negative group （51.5%, P=0. 001）. The VEGF positive rate of the HIF-2-α-positive group was 89. 8%, significantly higher than that of the HIF-1-α-negative group （26. 3%, P =0. 001 ）. The MVD of the 64 HIF- 1α, HIF-2α, and VEGF positive samples was 697, significantly higher than that of the 13 HIF-1α, HIF- 2α, and VEGF negative samples （391, P =0. 001 ）. The MVD of the HIF-2α positive samples was 678 ± 324, significantly higher than that of the HIF-2α negative samples （383 ±293, P =0. 001 ）. The MVD of the VEGF positive samples was 692 ±325, significantly higher than that of the VEGF negative samples （384 ±269, P =0. 001 ）. Spearman correlation analysis showed that MVD was strongly positively correlated with HIF-2α and VEGF. Mann-Whitney U test showed that HIF-1α and HIF-2α were not correlated with the staging of CCRCC. Conclusion HIF-2α is expressed more frequently in sporadic CCRCC than HIF-1α. Both HIF-1α and HIF-2α upregnlate the VEGF expression and angiogenesis, especially HIF-2α.

关 键 词：肾肿瘤 缺氧诱导因子 内皮生长因子 

分 类 号：R737.11[医药卫生—肿瘤]