The Expression Of Survivin And MMP-9 And Their Relationship In Eutopic Endometrium Of Endometriosis

Objective: To investigate the significance of survivin and MMP-9 expression and their relationship in the eutopic endometrium of patients with endometriosis, exploring the role of the eutopic endometium playing in the pathogenesy and the development of endometriosis.Methods: The women recruited in this study were all accepted the operations(laparoscopy or laparotomy) in the department of Gynecology in the second hospital of Tianjin Medical University from June,2000 to March,2007. Endometriosis was identified during laparoscopy or laparotomy in women consulting for endometrial cyst and/or pelvic pain and confirmed by histopathologists after operations. Patients with endometriosis (n = 80, mean age = 42.5±4.7 years) had no other pelvic condition. 47 women were in the proliferative phase and 33 women were in the secretory phase of their menstrual cycles. The stage of endometriosis was determined according to the revised classification of the American Society for Reproductive Medicine (American Fertility Society, 1996), Four had endometriosis stageⅠ, 25 endometriosis stageⅡ, 44 endometriosis stageⅢand 7 endometriosis stageⅣ. Control group (n = 20, mean age = 43.1±4.3 years) were patients acquiring operations the same period for hysteromyoma and exhibiting no visible evidence of endometriosis upon laparoscopy or laparotomy. Seven patients were in the proliferative phase and 13 were in the secretory phase of their menstrual cycles. The immunohistochemical method was used to determine the expression of survivin and MMP-9 in the eutopic endometrium, both the endometriosis group and the control group. Image-Pro Plus6.0 (IPP), the special-purpose system for quantitative measurement of medical images, was used to assay the quantitative of survivin and MMP-9 expression.Results: Survivin and MMP-9 were both expressed only in the cytoplasm, none of nuclei expressing was observed. The expression levels of survivin and MMP-9 in EMs group were significantly higher than in normal eutopic endometrium(P< 0.001), and both of them expressed mainly in endometrial glandular cell,significantly more than in extracellular matrix(P<0.05). Survivin expression of EMs group in different menstrual cycle had no difference (P>0.05),while the expression of the normal endometrium in the secretory phase was higher than in the proliferative phase (P< 0.05). MMP-9 expression had no difference between the secretory phase and the proliferative phase in both groups(P> 0.05). Besides, in both the secretory phase and the proliferative phase, survivin expression in EMs group was higher than in the control group (P<0.001), while there had no difference of MMP-9 expression been found between two groups in secertory phase(P=0.137). Survivin expression in endometriosis stageⅡwere higher than the stageⅢ(P=0.021), there had no difference of survivin expression within other stages(P> 0.05).While MMP-9 expression had no difference among all the endometriosis stages(P>0.05). There was a close relationship between survivin and MMP-9 expression levels in 80 eutopic endometrium of endometriosis (r=0.262, P=0.019).Conclusions: The overexpression and close relationship of survivin and MMP-9 highlight the synergism between survival and invasion of endometriotic cells contributing to the establishment of endometrial glands and stroma at ectopic sites and facilitate the futher development of endometriosis. In our study, no significant difference of the expression of survivin and MMP-9 was observed in different menstrual cycle phases or endometriosis stages(except that the survivin expression in stageⅡwas higher than in the stageⅢof endometriosis). It may suggest that overexpression of survivn and MMP-9 is an earlier event in the progression of endometriosis,and once with endometriosis both of their expression would keep on overexpressing, free of the influence of the menstrual cycle and severity of endometriosis. On the whole,the study may provide experimental basis for the therapy of endometriosis aimming to modify the biological characters of eutopic endometrium,while survivin and MMP-9 may be good marker for therapy for etiological treatment of endometriosis.