HIF-1α在结外鼻型NK/T细胞淋巴瘤血管生成中的作用及意义

Angiogenic effect of HIF-1α on extranodal nasal-type NK/T-cell lymphoma

目的:研究缺氧诱导因子-1α(HIF-1α)在结外鼻型NK/T细胞淋巴瘤血管生成中的作用及意义。方法:采用免疫组化法检测50例人结外鼻型NK/T细胞淋巴瘤中HIF-1α、血管内皮生长因子(VEGF)和血管内皮生长因子受体2(VEGFR2)的表达情况,用CD34单克隆抗体标记血管内皮细胞,并计算肿瘤微血管密度(MVD),用SPSS 13.0软件分析HIF-1α与VEGF、VEGFR2及肿瘤MVD的相关性。结果:(1)50例中有39例(78%)肿瘤细胞HIF-1α阳性,27例(54%)VEGFR2阳性,与淋巴结反应性增生组织中淋巴细胞的表达情况比较均有显著差异(P<0.05);(2)HIF-1α蛋白阳性表达组VEGF和VEGFR2的阳性表达率分别为72%和64%,明显高于HIF-1α蛋白阴性表达组(P<0.05);(3)HIF-1α、VEGFR和VEGFR2蛋白表达与肿瘤MVD相关(P<0.01);(4)15例伴有血管中心性浸润的结外鼻型NK/T细胞淋巴瘤病例均表达HIF-1α。结论:HIF-1α可促进结外鼻型NK/T细胞淋巴瘤肿瘤血管生成,其作用机制可能与VEGF/VEGFR2通路有关。

AIM： To study the angiogenic effect of hypoxia inducible factor 1α（HIF-1α） and its significance on human extranodal nasal-type NK/T-cell lymphoma.METHODS： The protein levels of HIF-1α,vascular endothelial growth factor（VEGF） and VEGF receptor 2（VEGFR2） in human extranodal nasal-type NK/T-cell lymphoma were detected by immunohistochemistry.Microvessel density（MVD） of the tumor tissues was determined by labeling of microvessel endothelium with CD34 antibody.The correlation between the expression of HIF-1α,VEGF and VEGFR2 and MVD was analyzed with SPSS 13.0 statistical software.RESULTS： The positive expression of HIF-1α was observed in 39 cases（39/50,78%） and the positive expression of VEGFR2 was 27 cases（27/50,54%） of human extranodal nasal-type NK/T-cell lymphoma.A statistical difference of HIF-1α and VEGFR2 expression between tumor tissues and normal lymphocytes in lymph node was observed（P〈0.05）.In the tumor tissues,the co-expression of VEGF or VEGFR2 with HIF-1α was 72% and 64%,respectively,significantly higher than that without HIF-1α co-expression（P〈0.05）.The expression of HIF-1α,VEGFR and VEGFR2 was positively correlated with MVD of the tumor tissues（P〈0.01）.HIF-1α was expressed in all 15 cases of extranodal nasal-type NK/T-cell lymphoma with angiocentric infiltration.CONCLUSION： HIF-1α may promote angiogenesis of extranodal nasal-type NK/T-cell lymphoma through VEGF/VEGFR2 signaling pathway.