基质金属蛋白酶MMP-9及其组织抑制剂TIMP-1在不同类型滋养细胞中的表达

Expression and clinical significance of matrix metalloproteinases(MMP-9) and its tissue inhibitors (TIMP-1) Bin gestational trophoblass

目的通过研究基质金属蛋白酶MMP-9及其组织抑制剂TIMP-1在不同类型滋养细胞中的表达,探讨预测滋养细胞疾病恶变和转移的可能性。方法应用链霉菌抗生物素蛋白-过氧化物酶免疫组织化学方法对20例正常早孕(<12周)绒毛组织、15例部分性葡萄胎、55例完全性葡萄胎、15例侵蚀性葡萄胎、8例绒毛膜癌组织中MMP-9、TIMP-1进行检测。结果(1)MMP-9在正常早孕绒毛组织、部分性葡萄胎、完全性葡萄胎、侵蚀性葡萄胎、绒毛膜癌中均有表达,但随着滋养细胞恶性程度的增加其表达显著升高,差异有显著性(χ2=26.421,P<0.0001);(2)TIMP-1在正常早孕绒毛组织均有表达,而在部分性葡萄胎、完全性葡萄胎、侵蚀性葡萄胎、绒毛膜癌中分别有6.67%、5.45%、6.67%、12.50%不表达,且随着肿瘤恶性程度的升高,其染色程度和染色细胞百分率减少,差异有显著性(χ2=9.575,P<0.05);结论MMP-9和TIMP-1与正常早孕滋养细胞的侵袭过程有关,MMP-9与TIMP-1比值的改变可能参与了滋养细胞疾病的恶变和转移,对临床早期预测滋养细胞疾病的恶变及预防性化疗有一定的参考意义。

Objective To study the expression of matrix metalloproteinases （MMP-9） and tissue inhibitors of metalloproteinases （TIMP-1） in human gestational trophoblasts and their correlation in predicting the malignant transformation and metastasis. Methods Immunohistochemical streptavidin-peroxidase （S-P） method was used to detect the expression of MMP-9, TIMP-1 in 20 cases of normal human cytotrophoblast cells, 15 cases of partial hydatidiform moles, 55 cases of complete hydatidiform moles, 15 cases of invasive moles and 8 cases of choriocarcinoma. Results （1） MMP-9 expression was detected in all types of trophoblastic cells, with the development of the malignant transformation the staining was markedly increased. （x^2=26. 421, P〈0. 0001）. （2） Each case of normal human cytotrophoblast cells showed expression of TIMP-1, but 6. 67 % of partial hydatidiform moles, 5.45% of complete hydatidiform moles, 6.67 % of invasive moles and 12.50 % of choriocarcinoma were negative. With the development of the malignant transformation the staining was decreased （x^2=9. 575, P〈0. 048）. Conclusion MMP-9 is involved in the invasion of the normal human cytotrophoblast cells, while TIMP-1 makes this invasion controllable. The invasion and metastasis may be caused by the change of MMP-9/TIMP-1. The ratio of MMP-9/TIMP-1 can be used as indicators to reference the stage of gestational trophoblastic disease development and to assess the prognosis and clinical therapy.