宫颈癌组织中新生淋巴管及肿瘤内环境因子在其淋巴转移中的作用

Role of lymphangiogenesis and environmental factors in cervical cancer in lymph node metastasis

目的探讨新生淋巴管及肿瘤内环境因子在宫颈癌淋巴结转移中的作用机理。方法采用免疫组化方法检测宫颈癌(60例)、宫颈上皮内瘤变(CIN 3,20例)及正常宫颈(20例)组织中D2-40的表达和宫颈癌组织中CXCR4和CCR7的表达,及在宫颈癌深肌层和浅肌层中的表达。检测宫颈癌盆腔淋巴结中基质细胞衍生因子1(SDF-1)及CCL21的表达。显微镜下观察D2-40阳性表达的癌边缘淋巴管结构及组织中正常淋巴管结构。结果宫颈癌组织中的D2-40表达量高于CIN3组织和正常宫颈组织(26.72±1.75vs.13.95±1.48和2.08±0.65)(P<0.01)。CXCR4和CCR7在宫颈癌组织呈高表达,但在正常宫颈组织中为阴性,CIN 3组织部分为弱阳性表达;SDF-1和CCL21在宫颈癌患者盆腔5组淋巴结表达阳性。新生淋巴管密度与宫颈癌直径有关,深肌层侵犯者的新生淋巴管密度较浅肌层侵犯者增加(P<0.01)。结论宫颈癌组织可诱导产生新生淋巴管。淋巴管内皮细胞产生淋巴管趋化因子受体。新生淋巴管与组织淋巴管交汇,是宫颈癌淋巴结转移的重要桥梁。SDF-1和CCL21的淋巴结高表达是募集肿瘤细胞重要的趋化因子。新生淋巴管与肿瘤细胞交互作用,使肿瘤细胞向淋巴管迁徙,发生淋巴结转移。

Objective To explore the role of lymphangiogenesis and environmental factors in cervical cancer in lymph node metastasis. Methods With immunohistochemical method, the expressions of D2-40 were detected in normal cervical tissues（20 cases）, the cervical cancer（60 cases） and cervical intraepithelial neoplasia（CIN 3,20 cases）. The expressions of CXCR4 and CCR7 in the cervical cancer and those of SDF-1 and CCL21 in pelvic lymph nodes were detected as well. The structures of lymphatic vessels at the edge of the tumor with 132-40 positive expression and in the normal tissues were observed by microscope. Results The expression of I）2-40 in cervical cancer was higher in cervical cancer than that in CIN and normal cervical tissues（26. 72±1.75 vs. 13. 95±1.48 and2. 08±0. 65）（P〈0. 01）. CXCR4 and CCR7 were highly expressed in cervical cancer, but negatively expressed in normal cervical tissues and weekly expressed in CIN 3 tissues. The expressions of SDF-1 and CCL21 in the pelvic lymph nodes were positive in cervical cancer cases. The density of lymphangiogenesis was related to the diameter of cervical cancer, which was higher in the cases with deep invasion of muscle layer than those of superficial muscle layer（P〈0.01）. Conclusion Cervical cancer tissues can induce the lymphangiogenesis. Lymphatic endothelial cells produce lymphatic chemokine receptors. The interaction of lymphangiogenesis and lymphatic vessels is the bridge of cervical lymph node metastasis. The overexpressed SDF-1 and CCL21 in lymph nodes are the lymphatic chemokines to raise tumor cells. The interaction of lymphangiogenesis and tumor cells promotes the migration of tumor cells and lymph node metastasis.