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The Expression Of Survivin And Cathepsin D In Normal And Adnormal Endometrium

Posted on:2006-11-05Degree:MasterType:Thesis
Country:ChinaCandidate:H X SunFull Text:PDF
GTID:2144360155453513Subject:Clinical Medicine
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Endometrial carcinoma was the one of the most common malignant tumors in female, its incidence being increasing in recent years.It's critically hazardous to human health. It has been proved that most of endometrial hyperplasia diseases are reversed, except for some of them capable of carcinogenesis.The mechanism of carcinogenesis of endometrial carcinoma in molecular level is mainly concerned with the abnormal expression of genes including oncogene, anti-oncongene, and DNA injured repairing gene. SVV ,a recently discoverable inhibitor of apoptosis protein, takes dual effects in restraining apoptosis and adjusting cell proliferation. It is also proved by exterior and interior experiment that SVV is able to inhibit apoptosis that all kinds of apoptosis inducing factors induce. The expression of SVV in actively proliferating developed tissue and tissue of tumor indicates that cell proliferation or differentiation is related to SVV. Inhibiting apoptosis is significant in the course of blood vessel moulding and neovascularization .Vascular endothelial growth factor(VEGF) induces angiogenesis through inhibiting endothelial cell apoptosis which is carried out by inducing SVV hypso-expression in ensothelial cell, Cath-D, a kind of aminosuccinic acid endopeptidase and cytolysosome protease which is regulated by estrogen,belongs to acid protease and exists in form of incompetent protein proenzyme and is activated through changing cell microenviroment or self-degradation. activated Cath-D has ability to excite the growth of tumor cells and decompose extracellular matrix(ECM) and solute cell adhesion, SVV and Cath-D that act on endometria through autocrine and/or paracrine mechanisms mediate and regulate growth and differentiation of endometria under control of estrogen and progestogen, The expression of SVV and Cath-D is different as the expression of ER is different in proliferative ,secretory endometrium and breast carcinoma, especially recently studies had observed SVV and Cath-D is highly expressed, carcinoma of endometrium and breast carcinoma are gonadal hormone-dependent tumor, therefore it is necessary to study the relation between the expression of SVV and Cath-D and the accessing of carcinoma of endometrium and precancerous lesion. Our present study was aimed at evaluating the expression of SVV and Cath-D in normal endometria, atypical hyperplasia of endometria and endometrial carcinoma, and then exploring new biochemical targets for differential diagnosis and treatment for endometrial diseases. The study included 85 patients treated by dilatation & curretage and hysterectomy from May 2002 to December 2004 at the department of Obstetrics and Gynecology in the Second Clinical Hospital of Jilin University, pathologically proved 10 cases of normal endometrium (Normal Group) ,ages (46.5±1.8),and 35 cases of atypical hyperplasia of endometria (Hyperplasia Group ), ages (45.7±1.1). In addition, there were also 50 cases of endometrial carcinoma (Endocarcinoma Group). Clinical stage and histological grade wasevaluated in the adenocarcinoma group according to FIGO's standard: 27 cases of First Stage,7 cases of Second Stage, 10 cases of Third Stage,6 cases of forth Stage; 20cases of G1, 16cases of G2, 14 cases of G3. All of them underwent hysterectomy, bilateral salpigo-oophorectomy and selected pelvic lymphadonectomy,ages(46.1 ±2.3). Three groups have no significant difference by comparing ages(P>0.05).All patients included in our study had not used any hormonal contraceptive medicine or devices three months before operation,and been excluded patient history including endocrine diseases of gynecology and genital duct inflammation.Immunohistochemical staining for SVV and Cath-D were performed by SP. The expression intensity was demonstrated with weakly positive (+),positive(++),strong positive(+++),and negative(-),and analysed with HPIAS-1000 color imaging analysis system. SPSS 13.0 statistical software was used for statistical analysis. The significance of differences between individual groups was assessed with x2-test. In the present study, we have detected that SVV and Cath-D are equally weaklly positive and furthermore have lower positive ratio in Normal Group. In our study, SVV in nucleus and/or cytoplasm of endomembrane epitheliogland in Hyperplasia Group demonstrates weakly positive or positive,positive ratio(51.43%) is much higher than Normal Group(100%).The significance of difference between them indicates that earlier endomembrane pathological changes can make SVV up-regulated,and infers that SVV possibly takes part in malignant transformation of endometria from lesion precancerous to carcinoma. Cath-D in cytoplasm of endomembrane epitheliogland in Hyperplasia Group demonstrates strongly positive and furthermore highly expressive(91.43%),is much higher than Normal Group(20%)and Endocarcinoma Group.The significance of difference among them(P<0.05)illustrates that excessive expression of Cath-D takes part in paraplasm and infers that Cath-D is possibly concerned with some cellular increasing protease activity and strongly expression of protease,or alteration of sub-cellular distribution mode of protease.It indicates that Cath-D plays a important role in the course of malignant transformation and proliferation of endomembrane cell. In our study, with aggravating degrees of pathological changes of endometria, tendency of positive ratio and expression intensity of SVV is gradually increasing. positive ratio of SVV in Endocarcinoma Group(68.00%) is much higher than Normal Group(10.00%).The significance of difference between them (P<0.05) is concerned with stages and grades of endocarcinoma and it's transformation.It indicates that SVV expression plays a importantly regulated role in cell proliferation,differentiation,invasion,metastasis of endocarcinoma,and clinic development . Cath-D expression in Endocarcinoma Group demonstrates positive or strongly positive,it's positive ratio(66.00%) is apparently higher than Normal Group(20.00%).The significance of difference between them (P<0.05) is also concerned with stages and grades of endocarcinoma and it's transformation.It indicates that excessive expression of Cath-D is possibly concerned with progression and transformation of endocarcinoma. Moreover,it has been discovered inour study that in 34 cases of Endocarcinoma Group which is positive in SVV expression,there are 29 cases(85.30%) positive in Cath-D expression; in 16 cases of Endocarcinoma Group which is negative in SVV expression,there are 4 cases(25.00%) positive in Cath-D expression.The significance of difference(P<0.05) between them demonstrates that SVV expression is concerned with Cath-D.It indicates that in the course of generation,invasion,and matastasis of endocarcinoma both SVV and Cath-D genes possibly have synergism including...
Keywords/Search Tags:SVV, Cath-D, atypical hyperplasia of endometria, endometrial carcinoma, immunohistochemistry
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