基质金属蛋白酶-9及基质金属蛋白酶组织抑制物-1表达失衡与宫颈癌局部肿瘤血管生成的关系

目的 :探讨基质金属蛋白酶 - 9(MMP 9)和基质金属蛋白酶组织抑制物 - 1(TIMP 1)在宫颈癌局部肿瘤血管生成中的作用。方法 :采用免疫组织化学SP法检测 75例早期宫颈癌 (ICC)、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮 (NCE)中MMP 9和TIMP 1的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )。结果 :从NCE组到CIN组再到ICC组 ,MMP 9的阳性表达率显著升高 (P <0 0 5 )而TIMP 1未见升高 (P >0 0 5 ) ,并且TIMP 1在ICC组的阳性表达率显著低于MMP 9(P <0 0 1)。MMP 9在ICC组中表达与MVD显著正相关 (r =0 2 87,P <0 0 5 ) ,而TIMP 1与MVD无显著相关性 (r=0 195 ,P >0 0 5 )。宫颈癌中MMP 9表达高于TIMP 1者 ,其MVD显著高于MMP 9表达低于TIMP 1者 (P <0 0 5 )。结论 :MMP 9和TIMP 1表达失衡可能在宫颈癌局部肿瘤血管生成中起重要作用 ,MMP 9表达增强而TIMP 1表达降低 ,其血管生成能力可能显著增强 ,但并非唯一决定因素。检测宫颈癌中MMP 9和TIMP 1表达对进一步了解宫颈癌局部血管生成情况有一定的应用价值。

The Association of Unbalanced Expression of MMP-9 and Their Inhibitor-TIMP-1with Regional Tumor Angiogenesis in Invasive Carcinoma of Cervix

Objective: To investigated the role of matrix metalloproteinase-9(MMP-9)and their inhibitor,tissue inhibitor of matrix metalloproteinase-1(TIMP-1) in regional tumor angiogenesis in early invasive carcinoma of cervix. Methods :The expression of MMP-9, TIMP-1,and microvessel density(MVD) labeled by CD 34 were detected by immunohistochemistry SP method in 75 cases of early invasive carcinoma of cervix(ICC),18 cases of cervical intraepithelial neoplasm(CIN) and 15 cases of normal cervical epithelium(NCE) remoted from tumor lesion. Results :The positive expression of MMP-9 increased remarkably from NCE to CIN,and then to ICC(P<0.05),but that of TIMP-1 did not increase. The positive expression of TIMP-1 in ICC was significantly lower than that of MMP-9(P<0.01). In ICC,MVD was positively related to the expression of MMP-9(r=0.287,P<0.05),but not to TIMP-1(r=0.195,P>0.05). The MVD in the cases of higher expression of MMP-9 and lower expression of TIMP-1 was remarkably higher than that in those with lower expression of MMP-9 and higher expression of TIMP-1(P<0.05). Conclusions :In invasive carcinoma of cervix,unbalanced expression of MMP-9 and TIMP-1 may play an important role during tumor angiogenesis. Over-expression of MMP-9 and lower expression of TIMP-1 may result in a remarkably development of tumor angiogenesis,but not the only decisive factor. Detection for expression of MMP-9 and TIMP-1 may be valuable to further understand the regional tumor angiogenesis in invasive carcinoma of cervix.