宫颈癌组织及血清血管内皮生长因子C表达及其与淋巴转移的相关性分析

Expression of vascular endothelial growth factor-C in cervical tissue and its correlation with lymphatic metastasis

目的探讨血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C)在宫颈癌组织和血清中的表达水平,及其与淋巴转移的相关性。方法宫颈癌患者28例为宫颈癌组,其中有淋巴结转移20例,无淋巴结转移8例;颈上皮内瘤变Ⅲ(cervical intraepithelial neoplasiaⅢ,CINⅢ)期患者18例为CINⅢ组;因子宫肌瘤切除子宫患者28例为正常宫颈组。采用ELISA法检测各组血清VEGF-C、VEGF受体-3(VEGF receptor-3,VEGFR-3)水平;免疫组织化学SP法测定组织中VEGF-C、淋巴管内皮透明质酸受体-1(lymphatic endothelial hyaluronic acid receptor-1,LYVE-1)表达情况及微血管密度(microvessel density,MVD)、淋巴管密度(lymphatic vessel density,LVD);Western blot法检测组织中VEGFR-3、LYVE-1蛋白表达情况。结果宫颈癌组血清VEGF-C[(62.19±16.67)ng/L]、VEGFR-3[(6.03±1.00)ng/L]高于正常宫颈组[(30.23±8.97)、(1.12±0.47)ng/L)和CINⅢ组[(33.76±9.41)、(1.81±0.33)ng/L](P<0.05),有淋巴结转移者VEGF-C[(76.54±15.62)ng/L]、VEGFR-3[(8.11±1.68)ng/L]高于无淋巴结转移者[(45.88±12.79)、(4.43±1.05)ng/L],差异均有统计学意义(P<0.05);宫颈癌组组织中MVD(14.68±2.56)、LVD(13.09±3.01)及VEGF-C、LYVE-1蛋白阳性表达率(67.86%、75.00%)高于正常宫颈组(6.04±1.15、9.58±1.47、28.57%、32.14%)和CINⅢ组(7.15±1.08、10.01±1.34、33.33%、55.56%)(P<0.05),有淋巴结转移者组织中MVD(17.67±2.11)、LVD(15.32±2.07)及VEGF-C、LYVE-1蛋白阳性表达率(87.50%、100.00%)高于无淋巴结转移者(10.83±1.59、11.12±1.98、60.00%、65.00%)(P<0.05);宫颈癌组组织中VEGFR-3(0.732±0.104)、LYVE-1蛋白表达(0.653±0.089)高于正常宫颈组(0.112±0.001、0.395±0.013)和CINⅢ组(0.467±0.045、0.505±0.033)(P<0.01),有淋巴结转移者VEGFR-3、LYVE-1蛋白表达(0.885±0.071、0.756±0.065)高于无淋巴结转移者(0.675±0.064、0.598±0.053)(P<0.05)。结论 VEGF-C在宫颈癌组织及血清中均存在表达升高,与淋巴结转移及淋巴管生成相关,可作为宫颈癌淋巴转移的评估指标。

Objective To investigate the expression of vascular endothelial growth factor-C （VEGF-C） in cervical tissue and its correlation with lymphatic metastasis. Methods Twenty-eight patients with cervical cancer were divided into lymphatic metastasis group （n= 20） and non-metastasis group （n= 8）. Eighteen patients with cervical intraepithelial neoplasia Ⅲ （CINⅢ） were as CINUI group, and another 28 patients receiving hysterectomy due to uterine fibroids were as normal cervix group. The levels of serum VEGF-C and VEGF receptor-3 （VEGFR-3） were detected by ELISA method. The levels of tissue VEGF-C, lymphatic endothelial hyaluronic acid receptor-1 （LYVE-1） expression, microvessel density （MVD） and lymphatic density （LVD） were detected by SP immunohistochemical assay. The expressions of VEGFR-3 and LYVE-1 protein were detected by Western blot method. Results The serum levels of VEGF-C and VEGFR-3 were significantly higher in cervical cancer group （（62.19 ±16.67）, （6.03 ± 1.00） ng/L） than those in normal cervix group （（30.23±8. 97）, （1. 12±0. 47） ng/L） and CINⅢ group （（33. 76±9.41）, （1. 81± 0.33） ng/L） （P〈0.05）, and were significantly higher in metastasis group （（76.54±15.62）, （8.11±1.68） ng/L） than those in non-metastasis group （（45. 885=12.79）, （4.43±1.05） ng/L） （P〈0.05）. The levels of MVD and LVD, and the positive rates of VEGF-C and LYVE-1 proteins were significantly higher in cervical cancer group（14.68±2. 56, 13. 09±3.01, 67.86%, 75. 00%） than those in normal cervix group （6.04±1. 15, 9. 58±1.47, 28.57%, 32. 14%） and CIN Ⅲgroup （7. 15±1. 08, 10. 01±1. 34, 33. 33%, 55. 56%） （P〈0.05）, and were significantly higher in metastasis group （17. 674.2.11, 15. 324.2.07, 87.50%, 100.00%） than those in non-metastasis group （10. 834±1. 59, 11. 12±1. 98, 60. 00%, 65. 00%） （P〈0.05）. The expressions of VEGFR-3 and LYVE-1 proteins were significantly higher in cervical cancer group （0. 7324.0. 104, 0. 6534.0. 089） than those in normal cervix group （0.112±0. 001, 0.3954.0. 013） and CINⅢ group （0. 467 ±0. 045, 0. 505 ±0. 033） （P〈0.01）, and were significantly higher in metastasis group （0. 885 ± 0. 071, 0. 756 ± 0. 065） than those in non-metastasis group （0. 676 ±0. 064, 0. 598±0. 053） （P〈0.05）. Conclusion VEGF-C increases in the tissue and serum of cervical cancer and is correlated with lymphatic metastasis and lymphangiogenesis, which could be used as an indicator for evaluating lymphatic metastasis in patients with cervical cancer.