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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 of heparanase (HPA) in cervical squamous cell carcinoma and its clinical significance. Methods 28 cases of normal cervical epithelium (NCE), 36 cases of cervical intraepithelial neoplasm (CIN) and 68 cases of squamous carcinoma of cervix (SCC) were detected by immunohistochemistry. (MVD) of CD34, lymphatic microvessel density (VEGF) labeled with VEGFR-3, and proliferation index (PI) of MIB-1 were detected. Results The expression levels of HPA in NCE, CIN and SCC groups were 0.0646 ± 0.0166, 0.0968 ± 0.0155 and 0.1175 ± 0.0212, respectively. From NCE to CIN to SCC, HPA expression was significantly increased (P <0.01). In CIN group, the MVD and LMVD of high HPA overexpression were significantly higher than those of low expression overexpression (P <0.05), while the expression of HPA was positively correlated with MVD and MVD in CIN group (MVD: r = 0.625, P = 0.000) : r = 0.380, P = 0.022), but not PI (r = 0.300, P = 0.075). In SCC group, the MVD of high HPA overexpression group was significantly higher than that of low overexpression group (P <0.05). HPA expression was positively correlated with MVD in SCC group (r = 0.330, P = 0.006) : r = 0.124, P = 0.314; PI: r = -0.077, P = 0.533). The expression of HPA in SCC group was closely related to pelvic lymph node metastasis and vascular invasion respectively. The expression of HPA in patients with cervical squamous cell carcinoma with pelvic lymph node metastasis and vascular invasion was significantly higher than those without pelvic lymph node metastasis and without vascular invasion (P <0.01) . The expression of HPA in invasive cervical squamous cell carcinoma was significantly higher than that in the superficial muscular layer (P <0.05). The survival rate of patients with high expression of HPA in cervical squamous cell carcinoma was significantly lower than that in the low expression group, but not statistically significant (log rank test, P = 0.0607). Conclusion HPA may play an important role in the development of cervical squamous cell carcinoma. Upregulation of HPA in CIN group may promote lymphangiogenesis. Upregulation of HPA in SCC group may promote angiogenesis and invasion and metastasis of cancer cells. HPA overexpression may be a negative prognostic factor in patients with cervical squamous cell carcinoma.