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目的了解血管内皮生长因子(VEGF)、成纤维细胞生长因子-2(FGF-2)、金属蛋白酶组织抑制剂-1(T1MP-1)、胰岛素样生长因子-2(IGF-Ⅱ)及葡萄糖转运蛋白-1(GLUT1)在不同时期婴幼儿血管瘤(HOI)及迅速消退的先天性血管瘤(RICH)和血管畸形病变组织中的表达水平,探讨其临床意义。方法结合临床资料对74例血管病变标本进行病理复检。ElivisionTM免疫组织化学二步法检测GLUT1、VEGF、FGF-2、IGF-Ⅱ和TIMP-1的表达水平。结果3个时期HOI脉管的内皮层均有GLUT1表达,RICH和血管畸形病变组织未见表达。VEGF、FGF-2、IGF-Ⅱ和TIMP-1在增殖期HOI组的阳性表达率分别为90.0%、85.0%、95.0%和45.0%;在消退期HOI组的阳性表达率分别为80.0%、100%、27.0%和80.0%;在消退后期组的阳性表达率分别为11.0%、56.0%、11.0%和22.0%;在RICH组的阳性表达率分别为25.0%、100%、75.0%和25.0%;在血管畸形组的阳性表达率分别为12.0%、8.0%、0和8.0%。增殖期、消退期HOI组和血管畸形组VEGF的阳性表达率比较,差异有统计学意义(X~2= 33.34,P<0.01);增殖期、消退期、消退后期HOI组和血管畸形组FGF-2的阳性表达率比较,差异有统计学意义(X~2=43.18,P<0.01);增殖期、消退期HOI组和血管畸形组IGF-Ⅱ的阳性表达率比较,差异有统计学意义(X~2=44.47,P<0.01);增殖期、消退期HOI组和血管畸形组TIMP-1的阳性表达率比较,差异有统计学意义(X~2=21.84,P<0.01)。RICH组FGF-2和IGF-Ⅱ的阳性表达率同血管畸形组比较,差异有统计学意义。结论①HOI的生长和消退是一个多因素参与的连续性过程,IGF-Ⅱ可能在HOI的自然消退过程中起主要的调控作用;②GLUT1可作为HOI同其他血管病变相鉴别的特异性指标,VEGF、FGF-2、IGF-Ⅱ和TIMP-1也是HOI、血管畸形和RICH相互鉴别的良好指标。
Objective To investigate the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), tissue inhibitor of metalloproteinase-1 (TMP- 1), insulin-like growth factor-2 (IGF- (GLUT1) in infantile hemangiomas (HOI) and rapidly resolving congenital hemangiomas (RICH) and vascular malformations in different stages of the disease, to explore its clinical significance. Methods 74 cases of pathological changes of blood vessels were retrospectively reviewed. ElivisionTM immunohistochemical two-step method was used to detect the expression of GLUT1, VEGF, FGF-2, IGF-II and TIMP-1. Results The expression of GLUT1 was detected in the endothelium of HOI vessels in three stages, but not in the tissues of RICH and vascular malformations. The positive rates of VEGF, FGF-2, IGF-Ⅱ and TIMP-1 in proliferating phase HOI were 90.0%, 85.0%, 95.0% and 45.0%, respectively. The positive expression rates of VEGF, FGF- 100%, 75.0% and 25.0% in the RICH group, respectively. The positive expression rates in the later regimen group were 11.0%, 56.0%, 11.0% and 22.0% %. The positive expression rates in vascular malformation group were 12.0%, 8.0%, 0 and 8.0% respectively. The positive expression rate of VEGF in HOI group and vascular malformation group in proliferative phase and receding phase was significantly different (X ~ 2 = 33.34, P <0.01). In proliferative phase, extinction phase and regression of HOI group and vascular malformation group, -2 (P <0.01). There was significant difference in the positive expression rates of IGF-Ⅱ between HOI group and vascular malformation group in proliferative phase and regression group (X ~ 2 = 44.47, P <0.01). The positive expression rate of TIMP-1 in proliferative and remission HOI group and vascular malformation group was significantly different (X ~ 2 = 21.84, P <0.01). The positive expression rates of FGF-2 and IGF-Ⅱ in the RICH group were significantly different from those of the vascular malformation group, the difference was statistically significant. CONCLUSION ① The growth and remission of HOI is a continuous process involving multiple factors. IGF-Ⅱ may play a major regulatory role in the spontaneous regression of HOI. ② GLUT1 can be used as a specific marker to differentiate HOI from other vascular diseases. VEGF, FGF-2, IGF-II and TIMP-1 are also good indicators of HOI, vascular malformation and RICH mutual identification.