Expression And Significance Of Pituitary Tumor Transforming Gene-1,Matrix Metalloproteinase-2 And Extracellular Matrix Metalloproteinase Inducer In Adenomyosis

Objectives:Adenomyosis is a commom benign disease of the uterus that has biological behaviour of malignant tumor.Despite its frequent occurrence,the precise aetiology is still not unknown.The objective of this study was to determine whether endometrial invasion involve activation of matrix metalloproteinase-2(MMP-2) by extracellular matrix metalloproteinase inducer(EMMPRIN) and pituitary tumor transforming gene-1 (PTTG1).Our aim is to provide important theroy for the pathogenesis of adenomyosis, which would provide an objective experiment evidence for the clinical treatment in adenomyosis.Methods:Experimental specimens were collected by the department of pathology in the general hospital in Tianjin Medical Unverisity from January 2006 to December 2007. Adenomyotic and eutopic endometria were obtained from 35 patients undergoing hysterectomy.Normal endometrial tissues were obtained from hysterectomy specimens from the general hospital and the second hospital in Tianjin Medical Unverisity.The hysterectomies had been performed to treat with CINⅡ-Ⅲor carcinoma in situ of cervix.All tissue were cut into 4-um sections.The rabbit anti-person polyclonal antibodies PTTG1,EMMPRIN,MMP-2 and tissue inhibitor of metalloproteinases-1(TIMP-1) were used by immunohistochemical staining.The data was analysed by SPSS software.Results:1.The positive expression levels of PTTG1,EMMPRIN and MMP-2 were low in the normal endometrium and high in the adenomyotic endometrium.The positive expression level of TIMP-1 was high in the normal endometrium and low in the adenomyotic endometrium.2.Expression of PTTG1 and MMP-2 had statistic differences in the adenomyotic endometrium,eutopic endometrium and normal endometrial tissue(p＜0.001).They were increased in the adenomyotic endometrium and eutopic endometrium than that of in the normal endometrium(p＜0.05),but there were no difference between the adenomyotic endometrium and eutopic endometrium(p＞0.05).3.Expression of EMMPRIN had statistic difference in the adenomyotic endometrium,eutopic endometrium and normal endometrial tissue(p＜0.001). EMMPRIN was increased in the adenomyotic endometrium than that of in the eutopic endometrium and normal endometrium(p＜0.001),but there was no difference between the normal endometrium and eutopic endometrium(p＞0.05).4.Expression of TIMP-1 had statistic difference in the adenomyotic endometrium, eutopic endometrium and normal endometrial tissue(p＜0.001).TIMP-1 was increased in the normal endometrium than that of in the adenomyotic endometrium(p＜0.01), but there was no difference between the eutopic endometrium and normal endometrium or adenomyotic endometrium(p＞0.05).5.PTTG1 expression had correlation with MMP-2 but had no correlation with EMMPRIN and TIMP-1.6.In the normal endometrium,the positive expression level of MMP-2 was related to that of TIMP-1(P＜0.01) negatively,but it was not related to that of EMMPRIN (p＞0.05) significantly.In the adenomyotic endometrium,the positive expression level of MMP-2 was related to that of EMMPRIN positively(P＜0.05),but it was not related to that of TIMP-1(p＞0.05).Conclusions:1.The high expression of MMP-2 in adenomyosis,which can make eutopic endometrial tissues have a greater capacity to invade and which can cause eutopic endometrium to invade myometrium,may be cause the development of adenomyosis.2.PTTG1 was overexpressed in adenomyosis and had positive correlation with MMP-2, suggesting that PTTG1 may contribute to endometrium infiltration and invasiveness through modulation of MMP-2 activity and expression.3.In the adenomyotic endometrium,there was remarkably positive correlation between EMMPRIN and MMP-2,which can help to induce a more high expression level of MMP-2,then the results suggest that adenomyotic endometrium may be more invasive and may play an importmant role in the pathogenesis of adenomyosis.4.In the normal endometrium,there were remarkably negative correlation and good concordance between MMP-2 and TIMP-1,which can help to maintain the normal state of endometrium.5.The high expression of MMP-2 and the low expression of TIMP-1 in the adenomyotic endometrium can lead to the high ratio of MMP-2/TIMP-1,suggesting that in the adenomyotic endometrium,the effect of TIMP-1 restraining the activity of MMP-2 may be take part in the development of adenomyosis.6.Artificially induction the expression of TIMP-1 or interruption the expression of EMMPRIN,PTTG1 and MMP-2 probably inhibits the pathogenesis of adenomyosis. This study may provide a new auxiliary way for therapy of adenomyosis.