血管内皮生长因子C表达与宫颈鳞状细胞癌局部淋巴管血管生成和浸润转移及预后的关系

目的 探讨血管内皮生长因子C（VEGF-C）表达与宫颈鳞状细胞癌局部淋巴管血管生成、浸润转移及预后的关系.方法 采用免疫组织化学法检测28例正常宫颈上皮、36例宫颈上皮内瘤变和68例宫颈鳞状细胞癌组织VEGF-C表达,同时检测血管内皮生长因子受体3（VEGFR-3）标记的微淋巴管密度、Ki-67标记的增殖指数和CD34标记的微血管密度.结果 VEGF-C在正常宫颈上皮组、宫颈上皮内瘤变组和宫颈鳞状细胞癌组的阳性表达率分别为21.43%、61.11%和72.06%,从正常宫颈上皮组到宫颈上皮内瘤变组及宫颈鳞状细胞癌,VEGF-C表达明显升高（P＜0.01）.在宫颈上皮内瘤变组,VEGF-C表达与微血管密度明显正相关（r=0.199,P=0.048）,VEGF-C阳性表达者微血管密度明显高于VEGF-C阴性表达者（F=4.112,P=0.049）.在宫颈鳞状细胞癌组,VEGF-C表达与微淋巴管密度显著正相关（r=0.288,P=0.017）,VEGF-C阳性表达者微淋巴管密度显著高于VEGF-C阴性表达者（F=6.488,P=0.013）.VEGF-C在宫颈鳞状细胞癌组表达与增殖指数及微血管密度均无显著相关性（增殖指数：r=0.085,P=0.489 微血管密度：r=0.181,P=0.139）.VEGF-C在宫颈鳞状细胞癌组表达与盆腔淋巴结转移、脉管浸润及生存率密切相关（P＜0.05）,而与患者年龄、国际妇产科协会（FIGO）分期、组织学分级及间质浸润深度无关（P＞0.05）.VEGF-C阳性表达者盆腔淋巴结转移及脉管浸润的发生率分别明显高于VEGF-C阴性表达者（P＜0.05）,而VEGF-C阳性表达者生存率明显低于VEGF-C阴性表达者（Log rank检验,P=0.0357）.结论 宫颈鳞状细胞癌VEGF-C过度表达可能促进局部淋巴管生成及肿瘤转移,可能提示预后不良.

Relation among expression of VEGF-C protein and regional lymphangiogenesis, angiogenesis, invasion, metastasis and prognosis in squamous cell carcinoma of cervix

Objective To examine the relation among the expression of vascular endothelial growth factor C (VEGF-C) and regional lymphangiogenesis, invasion, metastasis and prognosis in squamous cell carcinoma of cervix.Methods The expression of VEGF-C, lymphatic microvessel density(LMVD) labeled by VEGFR-3, proliferation index (PI) of cancer cells labeled by Ki-67 and microvessel density (MVD) labeled by CD34 in 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 method. Results The positive rates of expressions of VEGF-C in NCE, CIN and SCC group were 21.43% , 61.11% and 72.06%, respectively. The positive expression of VEGF-C increased remarkably from NCE to CIN and SCC accordingly ( P ＜ 0. 01 ). The expression of VEGF-C in CIN significantly related to MVD ( r =0. 199, P =0. 048). The MVD in the cases with positively expressed VEGF-C in CIN was significantly higher than that with negatively VEGF-C expressed (F =4.112, P = 0. 049 ). The expression of VEGF-C in SCC significantly correlated with LMVD(r=0.288,P=0.017), but not with PI(r=0.085, P=0.489) and MVD(r=0. 181, P=0. 139). The LMVD in the cases with positively expressed VEGF-C in SCC was remarkably higher than that with negatively VEGF-C expressed ( F =6.488, P =0. 013 ). The expression of VEGF-C in SCC significantly related to pelvic lymph node metastasis, intravascular infiltration and survival rate (P ＜0.05 ), but not to patients' age, FIGO staging, histological grading, and depth of stroma infiltration (P ＞0.05 ). In the cases with VEGF-C positive expression in SCC group, the rate of pelvic lymph node metastasis and intravascular infiltration was significantly higher than that in those without the conditions mentioned above ( P ＜0.05 ). The patients' survival rate in the VEGF-C positively expressed cases in SCC group was significantly lower compared with the negative cases ( log rank test, P = 0.0357 ). Conclusion The overexpression of VEGF-C in SCC may result in rapid regional lymphangiogenesis and tumor metastasis, showing a bad prognosis.