鼻咽纤维血管瘤组织中VEGF，Flt-1，Flk-1，PCNA和CD34表达的实验研究
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摘要
目的本实验运用免疫组化法检测鼻咽纤维血管瘤(juvenile nasopharygealangiofibroma,JNA)组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮生长因子受体1/fms样酪氨酸激酶1(VEGFreceptor-1/fms-like tyrosine kinase-1,Flt-1)、血管内皮生长因子受体2/胎肝激酶1(VEGF receptor-2/fetal liver kinase-1,Flk-1)、增殖细胞核抗原(proliferating cellnuclear antigen,PCNA)和CD34的表达,并比较其与血管畸形中上述因子表达的差异,从分子水平探讨鼻咽纤维血管瘤与血管畸形的区别。
方法临床收集28例鼻咽纤维血管瘤标本,20例眶内海绵状血管瘤标本(经光镜下筛选均为血管畸形)及10例鼻内正常组织的标本,利用免疫组织化学法分别检测VEGF、Flt-1、Flk-1、PCNA和CD34表达,分析三组间数据有无差异,并分析JNA组织中VEGF、Flt-1和Flk-1三者间表达的相关性。
结果VEGF、Flt-1、Flk-1在JNA血管内皮细胞中的阳性表达率分别为96.4%(27/28)、100%(28/28)、100%(28/28),高于眶内海绵状血管瘤组织的10%(2/20)、40%(8/20)、45%(9/20),差别具有统计学意义(P<0.05),并且三者在JNA中的表达有相关性(P<0.05)。JNA组织中CD34标记的平均微血管密度(microvessel density,MVD)为(49.3±9.1)/高倍视野,高于眶内海绵状血管瘤的(29.1±6.7)/高倍视野,差别具有统计学意义(P<0.05)。PCNA在血管内皮细胞中的表达JNA(阳性率10.7%)与眶内海绵状血管瘤(阳性率0%)无差异(P>0.05),PCNA在间质细胞中的表达JNA(阳性率100%)显著高于眶内海绵状血管瘤(阳性率0%)(P<0.05)。
结论VEGF、Flt-1和Flk-1在JNA组织中的表达明显高于血管畸形,并且三者间的表达正相关,提示它们参与JNA的血管生成,并在这个过程中相互作用,从而促进JNA的发生、发展,提示JNA的本质为真性血管瘤。VEGF、Flt-1和Flk-1可作为区分血管瘤和血管畸形的标志物。
Objective To investigate the nature of juvenile nasopharygeal angiofibroma(JNA) through compared the differences of vascular endothelial growth factor(VEGF), VEGF receptor-1/ fms-like tyrosine kinase-1(VEGFR-l/Flt-1),VEGF receptor-2/ fetal liver kinase-1(VEGFR-2/Flk-l),proliferating cell nuclear antigen(PCNA) and CD34's expression between hemangioma and vascular malformation.
Methods 28 cases of JNA,20 cases of orbital cavernous hemangioma(all of these were sorted by microscope as vascular malformation) and 10 cases of chronic rhinosinusitis were studied respectively by immunohistochemical S-P methods,to detected the expression of VEGF,Flt-1,Flk-1,PCNA and CD34,and the correlation between the expression rates of VEGF,Flt-1 and Flk-1 was also analyzed.
Results The positive rates of VEGF,Flt-1,Flk-1 expression in the endothelial cells of JNA were 96.4%(27/28),100%(28/28),100%(28/28),higher than those in orbital cavernous hemangioma which were 10%(2/20),40%(8/20),45%(9/20), there were significant difference(P＜0.05).The average microvessel density(MVD) marked by CD34 in JNA was(49.3±9.1)/HPF(high power field),higher than orbital cavernous hemangioma which was(29.1±6.7)/HPF,there were significant difference (P＜0.05).The PCNA expression in the endothelial cells of JNA and orbital cavernous hemangioma were both positive,there were no significant difference (P＞0.05).The PCNA expression in stromal cells of JNA were positive(100%),the PCNA expression in stromal cells of orbital cavernous hemangioma were negative, there were extraordinary signifycant difference(P＜0.05).
Conclusion The expression of VEGF,Flt-1 and Flk-1 in JNA were higher than those in orbital cavernous hemangioma,and there was a correlation between the expression of VEGF,Flt-1 and Flk-1 in JNA.This showed us the expression of VEGF, Flt-1,Flk-1 may be the important factors and play a crucial role in the development of JNA,the nature of JNA could be a hemangioma.The expression of VEGF,Flt-1 and Flk-1 could be an effective sign to differentiate hemangioma and vascular malformation.
方法临床收集28例鼻咽纤维血管瘤标本,20例眶内海绵状血管瘤标本(经光镜下筛选均为血管畸形)及10例鼻内正常组织的标本,利用免疫组织化学法分别检测VEGF、Flt-1、Flk-1、PCNA和CD34表达,分析三组间数据有无差异,并分析JNA组织中VEGF、Flt-1和Flk-1三者间表达的相关性。
结果VEGF、Flt-1、Flk-1在JNA血管内皮细胞中的阳性表达率分别为96.4%(27/28)、100%(28/28)、100%(28/28),高于眶内海绵状血管瘤组织的10%(2/20)、40%(8/20)、45%(9/20),差别具有统计学意义(P<0.05),并且三者在JNA中的表达有相关性(P<0.05)。JNA组织中CD34标记的平均微血管密度(microvessel density,MVD)为(49.3±9.1)/高倍视野,高于眶内海绵状血管瘤的(29.1±6.7)/高倍视野,差别具有统计学意义(P<0.05)。PCNA在血管内皮细胞中的表达JNA(阳性率10.7%)与眶内海绵状血管瘤(阳性率0%)无差异(P>0.05),PCNA在间质细胞中的表达JNA(阳性率100%)显著高于眶内海绵状血管瘤(阳性率0%)(P<0.05)。
结论VEGF、Flt-1和Flk-1在JNA组织中的表达明显高于血管畸形,并且三者间的表达正相关,提示它们参与JNA的血管生成,并在这个过程中相互作用,从而促进JNA的发生、发展,提示JNA的本质为真性血管瘤。VEGF、Flt-1和Flk-1可作为区分血管瘤和血管畸形的标志物。
Objective To investigate the nature of juvenile nasopharygeal angiofibroma(JNA) through compared the differences of vascular endothelial growth factor(VEGF), VEGF receptor-1/ fms-like tyrosine kinase-1(VEGFR-l/Flt-1),VEGF receptor-2/ fetal liver kinase-1(VEGFR-2/Flk-l),proliferating cell nuclear antigen(PCNA) and CD34's expression between hemangioma and vascular malformation.
Methods 28 cases of JNA,20 cases of orbital cavernous hemangioma(all of these were sorted by microscope as vascular malformation) and 10 cases of chronic rhinosinusitis were studied respectively by immunohistochemical S-P methods,to detected the expression of VEGF,Flt-1,Flk-1,PCNA and CD34,and the correlation between the expression rates of VEGF,Flt-1 and Flk-1 was also analyzed.
Results The positive rates of VEGF,Flt-1,Flk-1 expression in the endothelial cells of JNA were 96.4%(27/28),100%(28/28),100%(28/28),higher than those in orbital cavernous hemangioma which were 10%(2/20),40%(8/20),45%(9/20), there were significant difference(P＜0.05).The average microvessel density(MVD) marked by CD34 in JNA was(49.3±9.1)/HPF(high power field),higher than orbital cavernous hemangioma which was(29.1±6.7)/HPF,there were significant difference (P＜0.05).The PCNA expression in the endothelial cells of JNA and orbital cavernous hemangioma were both positive,there were no significant difference (P＞0.05).The PCNA expression in stromal cells of JNA were positive(100%),the PCNA expression in stromal cells of orbital cavernous hemangioma were negative, there were extraordinary signifycant difference(P＜0.05).
Conclusion The expression of VEGF,Flt-1 and Flk-1 in JNA were higher than those in orbital cavernous hemangioma,and there was a correlation between the expression of VEGF,Flt-1 and Flk-1 in JNA.This showed us the expression of VEGF, Flt-1,Flk-1 may be the important factors and play a crucial role in the development of JNA,the nature of JNA could be a hemangioma.The expression of VEGF,Flt-1 and Flk-1 could be an effective sign to differentiate hemangioma and vascular malformation.
引文
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[2]Sun Y,Wu ZY,Expression of PCNA、VEGF and bFGF in endothelial cells of juvenile nasopharygeal angiofibroma[J].J Clin Otorhinolaryngol,2006,20(23):1076-1078.
[3]Mullien J B,Glowacki J.Hemangiomas and vascular malformation in infant s and children:a classification based on endothelial characteristics.Plast Reconst Surg,1982,69:412-422.
[4]Sternberg S.Diagnostic Surgical Pathology[M].Fourth Edition.Lipincott Williams and Wilkins 2004,1455-1456.
[5]Liang JG,Yi ZX,Liang P.The nature of juvenile nasopharyngeal angiofibroma[J].Otolaryngol Head Neck Surg,2000,123:475-481.
[6]王毅,金国安,金明哲,等.血管内皮生长因子在血管瘤及血管畸形中的表达[J].中华小儿外科杂志,2002,23(4):380-381.
[7]Chang J,Most D,Bresnick S,et al.Proliferative hemangiomas:analysis of cytokine gene expression and angiogenesis[J].Plast Reconstr Surg,1999,103:1-9.
[8]Takahashi K,Mulliken JB,Kozakewich HP,et al.Celluar markers that distinguish the phase of hemagioma during infancy and childhood[J].J Clin Inveest,1994,93(6):2357-2362.
[9]Bielenherg DR,Bucana CD,Sanchez R,et al.Progressive growth of infantile cutaneous hemangiomas is directly correlated with hyperplasia and angiogenesis of adjacent epidermis and inversely correlated with expression of the endogenous angiogenesis inhibitor,INF-beta[J].Int J Oncol,1999,14(3):401-408.
[10]陈星,齐政,等.VEGF及受体与早期宫颈癌淋巴转移机制的研究进展.国外医学妇产科学分册,2005,32(5):323-325.
[11]Witte L,Hicklin DJ,Zhu Z,et al.Monoclonal antibodies targeting the VEGF receptor-2(Flk-1/KDR) as an antiangiogenic therapeutic strategy[J].Cancer Metastasis Rev,1998,17(2):155-161.
[12]Ai JH,Zheng SG,Vascular endothelial growth factor receptor-1 promotes migration and invasion of hepatocellular carcinoma cell lines[J].Immunological Journal,2008,24(4):430-437.
[13]Huckle WR,Roche RI,et al.Post-transcriptional control of expression of sFlt-1,an endogenous inhibitor of vascular endothelial growth factor[J].J Cell Biochem,2004,93(l):120-132.
[14]Lin ZR,Zhang CR.Current advancement of soluble VEGF receptor 1 in corneal angiogenesis[J],Chinese Ophthalmic Research,2008,26(3):238-240.
[15]Pasyk KA.Quantitive evaluation of mast cells in celularly dynamic and adynaric vascular mallmation[J].Plast Recomstr Surg,1984,23:69-73.
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