血管内皮生长因子和基质金属蛋白酶-9在宫颈癌演进中与微血管密度的关系及其意义

Relationship and its significance between VEGF, MMP-9 and microvessel density in progression of cervical carcinoma

目的探讨VEGF和MMP-9在宫颈癌的演进过程中其表达与局部微血管生成间及临床病理参数间的关系。方法采用免疫组化SP法检测40例宫颈浸润癌(ICC)、52例宫颈上皮内瘤样病变(CINⅠ、Ⅱ、Ⅲ)和15例正常宫颈上皮(NCE)组织中VEGF和MMP-9的表达并检测其中微血管密度(MVD),分析VEGF和MMP-9在宫颈癌的演进过程中与MVD的关系。结果NCE、CIN及ICC组中MVD值分别为(12.31±3.82)、(35.66±6.35)和(48.19±10.82),逐渐升高,各组比较差异有显著性(P<0.01)。VEGF、MMP-9在NCE、CIN、ICC中的阳性表达率分别为0%、19.23%;67.50%、13.33%;42.31%、77.50%,逐渐升高,各组比较差异有显著性(P<0.05);在CIN和ICC中,当VEGF、MMP-9均呈阳性表达时,MVD值(50.33±11.22),显著较VEGF、MMP-9均呈阴性表达时的MVD值(25.06±7.63)高(P<0.01)。VEGF和MMP-9的表达有正相关性(rs=0.284,P<0.05)。结论微血管生成及VEGF、MMP-9参与宫颈癌发生、发展的全过程;VEGF及MMP-9在宫颈癌微血管生成中起正性调节及协同作用;MVD值升高提示宫颈癌侵袭转移潜能增加,VEGF、MMP-9可作为预测宫颈癌转移的生物学指标。

[Objective] To explore the correlation between the expression of vascular endothelial growth factor （VEGF）, matrix metalloproteinase-9（MMP-9） and local microvessel angiogenesis and clinical pathologic features in the course of gradual progression in cervical carcinoma, in order to provide reliable theoretical foundation for the study of anti-angiogenesis drugs and matrix metalloproteinase inhibitors. [Methods] The expression of VEGF, MMP-9, and MVD labeled by CD34 in 40 cases of ICC, 52 cases of CIN Ⅰ,Ⅱ,Ⅲ and 15 cases of normal cervical epithelium（NCE） were detected by immunohistochemical streptavidin-biotin-peroxidase （SP） method. [Results] The values of MVD in NCE, CIN and ICC group were （12.31±3.82）, （35.66±6.35）, （48.19±10.82） respectively, showing a significant difference between any of the two groups（P〈0.01）. The positive rates of VEGF and MMP-9 expression in NCE, CIN, ICC group were 0%, 19.23%, 67.50% and 13.33%, 42.31%, 77.50% respectively, showing a significant difference between any of the two groups（P〈0.05）. In ICC, CIN group, the value of MVD was （50.33±11.22） in both high positive expression cases of VEGF, MMP-9, and was significantly higher than that in both negative expression cases of VEGF, MMP-9, its value of MVD was （25.06±7.63） （P 〈0.01）. The expression of VEGF was positively correlated with the expression of MMP-9（rs=0.284, P 〈0.05）. [Conclusions] Angiogenesis and VEGF, MMP-9 are involved in the development of cervical carcinoma. VEGF, MMP-9 play positive-regulation in the angiogenesis of cervical carcinoma. The increase of MVD indicates the increased potential of invasion and metastasis in cervical carcinoma. VEGF, MMP-9 may be used as prognostic indexes of metastasis of cervical carcinoma.