乙酰肝素酶表达与宫颈鳞癌组织微血管微淋巴管生成、癌细胞增殖、浸润转移及预后的关系  

Relationship between Expression of Heparanase Protein and Angiogenesis,Lymphangiogenesis,Cancer Cell Proliferation,Invasion,Metastasis and Prognosis in Squamous Cell Carcinoma of Cervix

作　　者：齐碧如[1] 江忠清[2] 连成瑛[3] 黄勉[1] 林岷 陈玉华[1] 刘兆董[3] 方娇宁[3] 

机构地区：[1]福建省福州市第一医院妇产科,350009 [2]福建医科大学附属第一医院妇科,350005 [3]福建省妇幼保健院妇产科,350001 [4]福建医科大学基础医学院生理学与病理生理学系,350004

出　　处：《中国医疗前沿》2011年第19期11-15,56,共6页China Healthcare Innovation

基　　金：福建省教育厅项目(编号:JA04210;JA03104);福州市科技局项目(编号:2007-S-124)

摘　　要：目的探讨宫颈鳞癌组织乙酰肝素酶(heparanase,HPA)表达及临床意义。方法采用免疫组织化学法检测28例正常宫颈上皮(normal cervical epithelium,NCE)、36例宫颈上皮内瘤变(cervical intraepithelial neoplasm,CIN)和68例宫颈鳞癌(squamous carcinoma of cervix,SCC)组织HPA的表达情况,并检测CD34标记的微血管密度(microvessel density,MVD)、VEGFR-3标记的微淋巴管密度(lymphatic microvessel density,LMVD)和MIB-1标记的增殖指数(proliferation index,PI)。结果 HPA在NCE、CIN及SCC组的表达水平分别为0.0646±0.0166、0.0968±0.0155及0.1175±0.0212。从NCE到CIN再到SCC,HPA表达水平显著升高(P<0.01)。在CIN组,HPA高表达者MVD及LMVD均分别显著高于低表达者(P<0.05),HPA在CIN组表达分别与MVD及LMVD显著正相关(MVD:r=0.625,P=0.000;LMVD:r=0.380,P=0.022),而与PI无关(r=0.300,P=0.075)。在SCC组,HPA高表达者MVD显著高于低表达者(P<0.05),HPA在SCC组表达与MVD显著正相关(r=0.330,P=0.006),而分别与LMVD及PI无关(LMVD:r=0.124,P=0.314;PI:r=-0.077,P=0.533)。HPA在SCC组表达分别与盆腔淋巴结转移及脉管浸润密切相关,宫颈鳞癌有盆腔淋巴结转移和脉管浸润者HPA表达水平显著高于无盆腔淋巴结转移及无脉管浸润者(P<0.01)。宫颈鳞癌突破深肌层间质浸润者HPA表达水平明显高于浸润深度在浅肌层间质以内者,但未达统计学意义(t=1.946,P=0.056)。宫颈鳞癌HPA高表达患者生存率明显低于低表达组,但未达统计学意义(log rank检验,P=0.0607)。结论 HPA可能在宫颈鳞癌的发生发展过程发挥重要作用。HPA在CIN组表达上调可能促进微淋巴管生成,在SCC组表达上调可能促进血管新生及癌细胞浸润转移。HPA过度表达可能是宫颈鳞癌患者的一个不良预后因素。Objective To investigate the expression and clinical significance of Heparanase（HPA） protein in invasive squamous cell carcinoma of cervix.Methods The expression of HPA protein,microvessel density（MVD） labeled by CD34,lymphatic microvessel density（LMVD） labeled by VEGFR3,and proliferation index（PI） of cancer cells labeled by MIB-1 protein in 28 cases of normal cervical epithelium（NCE）,36 cases of cervical intraepithelial neoplasm（CIN） and 68 cases of squamous cell carcinoma of cervix（SCC） were detected by immunohistochemistry method.Results The expression of HPA was 0.0646±0.0166 in NCE,0.0968±0.0155 in CIN and 0.1175±0.0212 in SCC group.The positive staining reaction of HPA increased remarkably from NCE to CIN,and then to SCC group,accordingly（P0.01）.In the cases with higher HPA expression in CIN group,the MVD and LMVD all were significantly higher than that in those with lower HPA expressed（P0.05）.The HPA expression in CIN group positively correlated with MVD and LMVD respectively（for MVD：r=0.625,P=0.000;for LMVD：r=0.380,P=0.022）,but not correlated with PI（r=0.300,P=0.075）.In the cases with higher HPA expression in SCC group,the MVD was significantly higher than that in those with lower HPA expressed（P0.05）.The HPA expression in SCC group positively correlated with MVD（r=0.330,P=0.006）,but not correlated with LMVD and PI（for LMVD：r=0.124,P=0.314;for PI：r=-0.077,P=0.533）.The expression of HPA in SCC closely correlated with pelvic lymph node metastasis and intravascular infiltration（P0.01）.In the cases with pelvic lymph node metastasis and intravascular infiltration,the positive staining reaction of HPA was significantly higher than that in those without the conditions mentioned above（P0.01）.The expression of HPA was higher in the cases with deeper stroma involvement than that in the cases without it,but the statistical significance has no difference（t=1.946,P=0.056）.The patients with higher expression of HPA in SCC group had lower sur

关 键 词：宫颈肿瘤 乙酰肝素酶 血管生成 淋巴管生成 肿瘤转移 免疫组织化学 

分 类 号：R364.7[医药卫生—病理学] R737.33[医药卫生—基础医学]