Expression Of Matrix Metalloproteinases And It's Tissue Inhibitors In Gestational Trophoblastic Disease And It's Clinical Significance

Objective: To study the expression of matrix metallopreteinases (MMP-2,9) and tissue inhibitors of metallopreteinases (TIMP-1,2) in human gestational trophoblastic disease and their correlation with clinic pathological parameters in predicting the malignant transformation and metastasis.Methods: Immunohistochemical streptavidin-peroxidase (S-P) method was used to detect the expression of MMP-2, MMP-9, TIMP-1, TIMP-2 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) No significant difference with MMP-2 expression in all cases. (X2=0.926, P=0.921)(2) MMP-9 expression was detected in all types of trophoblastic cells, with the development of the malignant transformation the staining was markedly increased.(X2=26.421, P=0.0001)(3) Each cases of normal human cytotrophoblast cells expression 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 thedevelopment of the malignant transformation the staining was decreased. (X2=9.575, P=0.048)(4) The expression of TIMP-2 in all cases has no significant difference. (X2=1.462, P=0.833)(5) In hydatidiform moles, the expression of MMP-9 correlated with age and times of curettage (rs=0.262 , P=0.028; rs=0.390, P=0.001) . The expression of TIMP-1 was decreased in women with the hydatidiform moles complicated theca lutein ovarian cyst, hyperemesis gravidarum, pregnancy-induced hypertension syndrome, higher -HCG serum values,and the longer time for negative-transition of HCG. TIMP-1 also assosciate with times of curettage in the hydatidiform moles.(6) No significant difference of MMP-9 expression in hydatidiform mole between malignant transformation and without malignant transformation. (Mann-Whitney U=116.0 , P=0.320) But much lower TIMP-1 expression in malignant transformation cases. (Mann-Whitney U=77.00, P=0.015)(7) In invasive moles no correlation was found among the MMP-9, TIMP-1 and the pathological types. (rs=0.196, P=0.485; rs=-0.495, P=0.061) But the expression of MMP-9 and TIMP-1 was significant difference between the malignant cases and without malignant cases. (Mann-WhitenyU=4> P=0.021 ; Mann-WhitenyU=5.5, P=0.01)(8) The expression of MMP-9 in choriocarcinoma was increased especially in matastasis cases,while the TIMP-1 was decreased in the same cases.Conclusion: MMP-2 and MMP-9 be involved in the invasion of the normal human cytotrophoblast cells, while TIMP-1 and TIMP-2 make this invasion controllable. MMP-9 and TIMP-1 probably be involved in invasion of the human gestational trophoblastic disease and angiogenesis. Upregulation of the MMP-9 and downregulation of the TIMP-1 with the malignancy degree in thetrophoblastic disease . The invasion and metastasis may 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, provide the evidence to assess the prognosis and clinical thearpy. The change of MMPs/TIMPs might be one reason of pregnancy-induced hypertension syndrome in the human gestational trophoblastic disease. MMP-2 and TIMP-2 might have no closely related to the invision of trophoblast. Human thorionic gonadotropin may play an important role in the expression of TIMP-1. The expression of MMP-9 correlated with age and times of curettage in hydatidiform moles.