The Expression And Clinical Significance Of The Matrix Metalloproteinase Inhibitor RECK In Endometriosis

Background: Endometriosis (EMs) is that endometrial tissue (glands and stroma) which has the function of growing appear in anywhere but in the uterine cavity and myometrium. The disease has variety of clinical manifestations, although histology is benign, there are prolifera-tion, invasion, metastasis , recurrence and so on , such theses vicious acts. For child-bearing age women, it is one of the most common diseases. The pathogenesis of endometriosis has a variety of doctrines, but the most widely accepted theory is the blood current cultivation. Counter-current of menstruation is very widespread among child bearing period of women, the incidence is as high as 76% ~ 90%, but the incidence of the endometriosis is only 10% to 20%, it indicates that counter-current of menstruation may be only incentives, and the acting such as adhesion, erosion, proliferation and differentiation similar to the biological behavior of tumors of the ectopic endometrium to ovarian and other pelvic organs and peritoneal is the key to its pathogenesis. The cultivation , erosion and growth of endometrial debris reflux-ing into the abdominal cavity need extracellular matrix (ECM) destruction and reconstruction. Degradation of ECM depends mainly on the serine protease, cysteine protease, caspase and matrix metalloproteinase (matrix met-alloproteinases, MMPs), that 4 kinds of hydrolase-like protein, and MMPs are a class of the more important, almost can degrade all extracellular ma-trix components, and is closely related to the invasion and metastasis of tumor cells. The study in recent years found that EMs patients likely to be impacted by matrix metalloproteinases (MMPs) and their specific tissue inhibitor (TIMP).Matrix metalloproteinases are a group of protease that can lead to the degradation of majority of extracellular matrix and various types of collagens,and are zinc- depen dent proteolytic enzymes, its activity determines the regulation of extracellular matrix degradation. When an error control mechanism of MMPs, extracellular matrix destructive degradation have been ex-cessive and too frequent, it would lead to the occurrence of many diseases and the deteriora-tion of the disease process (such as endometriosis, cancer, arthritis, etc.). Among them , MMP-2 and MMP-9 belong to gelatinases, mainly play a role with typeⅣcollagen as sub-strate, often exist in the form of non-activity, and in malignant tumors ,often be acti-vated,expressed highly .RECK (reversion inducing cysteine rich protein with Kazal motifs) is a newly discovered tumor suppressor gene, it has a unique fuction of inhibiting expression and activity of matrix metalloproteinase (matrix matalloproteinases, MMPs), is a matrix metalloproteinase inhibitor. It is known by now that RECK gene at least suppress three kinds of MMP at the level of post-transcriptional: MMP-2, MMP-9 and MT1-MMP, thereby inhibit angiogenesis and me-tastasis of tumor further. Studies have shown that RECK gene expression in liver cancer, pan-creatic cancer, breast cancer, lung cancer was negatively correlated to tumor invasiv- eness,and patients with higher expression of RECK gene often have better prognosis significantly than patients with low expression. Therefore it is considered that the RECK gene is a new tumor suppressor gene, its mechanism may be related to inhibition of the wide range of MMPs.Objective: To investigate the expression and clinical significance of RECK, MMP-2, MMP-9 and MVD in ectopic endometrium of the EMs.Method: Immunohistochemical S-P was used to detect the expression of RECK, MMP-2, MMP-9 in 48 cases of ectopic endometrial tissue, 31 cases of normal endometrial tissue, at the same time to observe microvessel density (MVD) in different organizations .The results: MMP-2, MMP-9, RECK were expressed mainly in the cytoplasm, rates of the positive expression in the ectopic endometrium respectively were: 89.6%, 79.2%, 43.8%, the positive expression rates in the normal endometrium were: 35.5 %, 19.4%, 87.1%, MMP-2, MMP-9 expression in ectopic endometrium was significantly higher than in normal endo-metrium, RECK expression in ectopic endometrium was significantly lower than the control group, there was a significant difference (P <0.05); RECK expression was negatively corre-lated to MMP-2, MMP-9 expression, (r =- 0.468, -0.320, P <0.05); MMP-2, MMP-9, RECK expression and clinical stage had no significant correlation (P> 0.05). MVD count in the ec-topic endometrium expressed as 17.55±4.82, in the normal endometrium for 8.79±2.45, compared the two groups were significantly different (P <0.05). MMP-2 expression and MVD was positively correlated (r = 0.783, P <0.05), MMP-9 expression and MVD was positively correlated too(R = 0.637 P <0.05), while RECK expression and MVD was a negative correla-tion (r =- 0.530 , P <0.05).Conclusion:1.In the EMs, RECK protein expression was significantly decreased, suggesting that in the ectopic endometrium the RECK gene expression was reduced, the lack of RECK promote the invasion of endometriotic cells,ability.2.That MMP-2, MMP-9 protein expression in ectopic endometrium was significantly in-creased, and MMP-2 protein, MMP-9 protein expression and clinical stages of EMs had no significant correlation ,shows the severity of the disease has nothing to do with the ag-gression, the ectopic tissues in various stages of the disease have the same invasion.3.Microvessel density (MVD) in ectopic endometrium was significantly higher in ectopic endometrium,it indicated that some factors led to the increasion of microvessel density (MVD). MMP-2, MMP-9 proteins in EMs with MVD count were positively correlated. It showed that the MMP-2, MMP-9 over-expression promoted the proliferation of blood vessels in EMs.4.In ectopic endometrium, the RECK protein expression decreased , and were nega-tively correlated with MMP-2 protein, MMP-9 protein and microvessel density (MVD) expression ,suggesting that the increasing expression of RECK provides a new way of thinking as a treatment method of EMs and a new EMs treatment drug develop- ment,and offers a new target for the treatment of EMs.