MMP-2/TIMP-2在妊娠滋养细胞疾病组织中的表达及意义

MMP-2/TIMP-2 expression in the trophoblasts of patients with gestational trophoblastic disease

目的探讨金属基质蛋白酶-明胶酶A(MMP-2)及其抑制剂(TIMP-2)在妊娠滋养细胞疾病发生、发展及预后中的作用。方法采用原位杂交、免疫组化法分别从mRNA、蛋白质水平检测MMP-2/TIMP-2在正常早孕绒毛及妊娠滋养细胞疾病中的表达。结果未恶性转化葡萄胎MMP-2低表达,TIMP-2高表达,恶性转化葡萄胎、侵蚀性葡萄胎、绒癌中MMP-2表达逐渐增强,TIMP-2表达相反。妊娠滋养细胞肿瘤组与正常绒毛、葡萄胎组相比,MMP-2、TIMP-2的表达均有显著性差异(P<0.01,P<0.001)。结论金属基质蛋白酶的激活与抑制比例失衡在妊娠滋养细胞疾病发展、浸润和转移中起重要作用。

Objectative To explore the role of matrix metaUoproteinase-2 （MMP-2） and tissue inhibitor of MMP-2 （TIMP-2） in the pathogenesis, development and prognosis ofgestational trophoblastic disease （GTD）. Methods In situ hybridization and imrnunohistochemistry were utilized for MMP-2/TIMP-2 mRNA and protein detection in normal chorion of women with early gestation, hydatidiform mole, invasive mole, or choricarcinoma. Results The results revealed that specific staining for mRNA and protein of MMP-2 and the expression of TIMP-2 was reduced in normal chorion of early gestation. In GTD ranging from hydatidiform mole, invasive mole to choricarcinoma, MMP-2 expression tended to increase while TIMP-2 expression underwent an invert change. The positivity rate of MMP-2 and TIMP-2 in gestational trophoblastic tumor group was higher than that of the normal chorion of early gestation group and hydatiform mole group （P〈0.05 and P〈0.001, respectively）. Conclusion A disrupted balance between the activation and inhibition of MMP-2 plays a critical role in the pathogenesis, progression and metastasis of GTD.