Expression And Clinical Significances Of Mel-CAM,Matrix Metalloproteinase-9 And Tissue Inhibitors Of Metalloproteinase-2 In Normal Villi And Gestational Trophoblastic Disease

Objective: To study the expression of melanoma cell adhesion molecule (Mel-CAM or CD146 or MUC18), matrix metalloproteinases-9 (MMP-9) and tissue inhibitors of metalloproteinases-2 (TIMP-2) in normal villi and gestational trophoblastic disease and to assess the relationship between their expression and malignant transformation of hydatidiform mole and the prognostic factors of gestational trophoblastic tumor.Method: Formalin-fixed paraffin sections of 30 cases of normal villi and 80 cases of complete hydatidiform mole (HM, 36 cases of complete mole that progressed to gestational tumor and 44 cases of complete mole that remitted spontaneously) and 76 cases of gestational trophoblastic tumor (37 cases of invasive hydatidiform mole and 39 cases of choriocarcinomas) obtained from the department of pathology Qilu hospital Shandong university from January 1981 to December 2001. The expression of Mel-CAM, MMP-9 and TIMP-2 were detected by immunohistochemical staining method and their clinical significances were analyzed.Results: Mel-CAM, MMP-9 and TIMP-2 protein were detected in normal villi and gestational trophoblastic disease .The expression of Mel-CAM and MMP-9 was remarkably elevated in malignant transforming mole than that in normal villi and non-malignant transforming mole (P=0.000; 0.020 respectively). There was no significant difference in TIMP-2 expression between normal villi and non-malignant transforming mole and malignant transformeing of hydatidiform mole (P=0.608). The sensitivity and specificity of Mel-CAM in predicting malignant transformation of hydatidiform mole was 71.05% and 78.57% respectively, the sensitivity and specificity of MMP-9 predicting malignant transforming of hydatidiform mole was 55.32% and 69.70% respectively. Mel-CAM and MMP-9 entered on the Equation of Logistic Regression, the odds ratio(OR) is 121.435. With the combination of Mel-CAM and MMP-9, The overall percentage of predicted of Mel-CAM and MMP-9 was 78.8%. The level of Mel-CAM and MMP-9 expression in trophoblastic tumor (IHM and CC) was significantly higher than that in the groups of normal villi and hydatidiform mole (P=0.001;0.001 respectively).The level of TIMP-2 was significantly lower in gestational trophoblastic tumor than that in normal villi and hydatidiform mole(P=0.000).The expression of Mel-CAM and MMP-9 were increased in late stage GTT than early stage disease (P=0.000;0.045 respectively) and correlated with the high risk score , while the TIMP-2 expression was decreased in late stage(P=0.002) and had no correlation with high risk score.Conclusion: Expression of Mel-CAM, MMP-9, TIMP-2 were correlated with the prognosis of gestational trophoblastic tumor. Mel-CAM and MMP-9 could predict the malignant transformation of complete hydatidiform mole.