骨巨细胞瘤缺氧诱导因子1α和VEGF表达及与肿瘤血管密度关系探讨

Expressions of HIF-1α and VEGF in giant cell tumor of bone and their relationship with tumor angiogenesis

目的:探讨缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)和血管内皮细胞生长因子(vascular endothelial cellgrowth factor,VEGF)在骨巨细胞瘤中的表达规律及与肿瘤血管密度的关系。方法:选用2003～2007年经手术切除并经病理证实为骨巨细胞瘤的51例患者的组织石蜡包块,病理分级(Jaffe标准)Ⅰ级15例,Ⅱ级17例,Ⅲ级19例,应用免疫组织化学方法,检测骨巨细胞瘤中HIF-1α、VEGF和CD34的表达,统计肿瘤微血管密度(microvessel density,MVD),检测骨巨细胞瘤HIF-1α、VEGF阳性与阴性标本中MVD并进行组间统计分析。结果:骨巨细胞瘤HIF-1α和VEGF总阳性率分别为62.7%(32/51)和71.4%(35/51),Ⅲ级骨巨细胞瘤HIF-1α和VEGF阳性表达率均显著高于I级和II级骨巨细胞瘤。HIF-1α与VEGF表达均阳性者28例,HIF-1α与VEGF表达均阴性者12例,HIF-1α与VEGF表达分布有相关一致性。骨巨细胞瘤MVD为25.7±4.2/高倍视野,Ⅲ级骨巨细胞瘤MVD(37.3±3.6/高倍视野)显著高于Ⅰ级骨巨细胞瘤(18.2±3.4/高倍视野)和Ⅱ级骨巨细胞瘤(19.4±2.6/高倍视野)。HIF-1α阳性骨巨细胞瘤MVD(32.2±4.2/高倍视野)显著高于HIF-1α阴性骨巨细胞瘤(14.7±2.5/高倍视野),VEGF阳性骨巨细胞瘤MVD(30.6±3.7/高倍视野)显著高于VEGF阴性骨巨细胞瘤(14.9±2.6/高倍视野)。结论:HIF-1α和VEGF表达与骨巨细胞瘤的病理分级相关,呈肿瘤特异性表达,与肿瘤血管生成密切相关。

Objective：To observe the expressions of hypoxia inducible factor-1α （HIF-1α） and vascular endothelial growth factor （VEGF） in giant cell tumor of bone （GCT） and their relations with tumor angiogenesis. Methods：The specimens from 51 GCT patients from 2003 to 2007 were included in the study.Among them 15 specimens were grade Ⅰ by Jaffe biological standard. 17 were grade Ⅱ and 19 were grade Ⅲ .The expressions of HIF-1α,VEGF and CD34 of GCT were studied by immunohistochemistry stain.The microvessal density （MVD） was counted by endothelial cells immunostained by anti-CD34 antibody. The MVDs of the specimens with positive or negative stain of HIF-1α or VEGF of GCT were calculated. Results：The positive rates of HIF-1α and VEGF in GCT were 62.7%（32/51） and 71.4%（35/51 ）respectively. The positive rates of HIF-1α and VEGF in GCT of grade Ⅲ were higher than those of grade Ⅰ or grade Ⅱ. Both HIF-1α and VEGF were positive in 28 specimens. Both HIF-1α and VEGF were negative in 12 specimens. The expressions of HIF-1α and VEGF were correlated. MVD of GCT was 25.7±4.2/every high-power field （HP）. The MVD in GCT of grade Ⅲ （37.3＋3.6/ I-IP）was higher than that of grade Ⅰ （18.2±3.4/HP）or grade Ⅱ （19.4±2.6/HP）. MVD in the specimens with HIF-1α positive stain （32.2± 4.2/HP） was higher than that with negative stain （14.7±2.5/HP）. MVD in the specimens with VEGF positive stain （30.6±3.7/HP） was higher than that with negative stain（14.9±2.6/HP）. Conclusion：The tumor special expressions of HIF-1α and VEGF in GCT were correlated with the biological grading and the angiogenesis of GCT.