The Expression Of Fibulin-5and Its Relationship With Angiogenesis In Epithelial Ovarian Tumor

BackgroudOvarian carcinoma is the third common malignancy in femalereproductive system.The early diagnosis of ovarian cancer is limited sincemost patients did not present typical symptoms at early stage,and werediagnosed with terminal cancers (FIGO stage III/IV). Although thetreatment technology in recent years is continuously improved,the5-yearsurvival rates of this disease have not obviously increased.Ovariancarcinoma is a serious threat to women’s lives and health for its highmortality.Therefore new treatment approaches are required to improve theprognosis for this disease.The poor prognosis of ovarian cancer isassociated with multifocal intraperitoneal dissemination accompanied byintense neovascularization.Angiogenesis is critical for the growth andmetastasis of solid tumours.Neovascular not only provide nutrients andoxygen for tumor growth,remove the metabolites,but also transmit tumorcells to other organ.All of those make it an important element for tumorgrowth,invasion and metastasis.And inhibiting angiogenesis could lead to early growth retardation of carcinamas.Therefore,therapies which targetssome critical link or important cytokines of the tumor angiogenesis processbecomes a new strategy for tumor therapy.For the comprehensive treatmentssuch as primary cytoreductive surgery and chemotherapy cannot obviouslyimprove the prognosis of ovarian cancer, antiangiogenesis therapy or couldbe the breakthrough to improve the prognosis of ovarian cancer.Fibulin-5is a66-kDa glycoprotein which is a new type of extracellularmatrix protein mapped in chromosome14q32.1.Fibulin-5contains sixcalcium-binding epidermal growth factor(EGF)-like(cbEGF) modules,inwhich there is an evolutionally conserved arginine-glycine-aspartic acid(RGD) motif.The RGD motif participates in mediation the interaction withcell surface integrins,including ανβ3,ανβ5and α9β1.Fibulin-5is one of themost important factors involved in embryonic development andorganogenesis.It can combine with tropoelastin,fibrillin-1and crosslinkedenzyme.This is crucial for the formation of elastic fiber,which is the mostimportant matrix for the blood vessel wall.It has been shown that fibulin-5could induce vascular smooth muscle cells proliferation and movement ininjuried blood vessels and could enhance the adhesion of endothelialcells.The deletion and mutation of fibulin-5gene could cause a variety oflesions,such as thoracic aortic aneurysm,cutis laxa,pelvic organ prolapse andpulmonary emphysema.The mRNA of fibulin-5could be detected in thenormal human heart, ovarian and colon tissue.However it was down-regulated in the majority of metastatic humanmalignancies,particularly in carcinomas of the lung,kidney,breast andcolon.In vitro and vivo studies confirmed that fibulin-5could controlvasculogenesis by affecting the expression of angiogenesis factors and theproliferation and migration of vascular endothelial cells.Fibulin-5alsoslowed down the mice tumor growth by preventing blood vessels fromsprouting.All of these showed that fibulin-5played an important part in thetumor procession and angiogenesis.Now the effects of fibulin-5on tumorcells’ biological behaviors and the regulatory mechanisms of theangiogenesis are not clear.It is still short of the study about fibulin-5inovarian cancer.Therefore,the investigation of fibulin-5expression inepithelial ovarian tumors and its relationship with angiogenesis will bebeneficial to the management of ovarian cancer.Objective1.To investigate the angiogenesis of epithelial ovarian tumors.2.To investigate the expression of fibulin-5in epithelial ovarian tumors.3.To investigate the relationship between fibulin-5and tumorangiogenesis in ovarian carcinomas.Methods1Date from89cases of epithelial ovarian tumors diagnosed at the FirstAffiliated Hospital of Chongqing Medical University were analyzed, and allof these cases had complete clinical and pathological informations. The blood flow signals of ovarian tumors were detected preoperatively by colorDoppler ultrasound and the resistance index (RI) was used for analysis.2. The expression of fibulin-5and CD34in89epithelial ovarian tumorpatients were detected by using immunohistochemical SP method afteroperation,then counted the microvessel density(MVD) with the endothelialcells which marked by CD34.The relationship between the expression offibulin-5and tumor biological behaviors were analysed by combining withclinical pathological parameters.3.The correlation among fibulin-5,MVD and RI in epithelial ovariancarcinomas were analysed by Spearman’s correlation analysis.Results1The median values of RI in ovarian carcinomas were significantlylower than that in benign tumors(P＜0.05),and it was negatively correlatedwith MVD(P＜0.05).2Fibulin-5proteins were mainly distributed in cell cytoplasm,positivestaining for yellow or tan.The positive rates of fibulin-5expression inovarian carcinomas were lower than that in benign epithelial ovariantumors（P＜0.05),but there was no difference between malignant andborderline tumors.The positive rates of fibulin-5expression in benign werehigher than that in borderline tumors(P＜0.05).The MVD amongbenign,borderline and malignant tumors showed ascendant trend,and ascompared between any two groups there were significant differences(P＜0.05).3The positive expression of fibulin-5in different clinical stage anddegree of differentiation had statistical significance in ovariancarcinomas,but there was no difference in different age groups andpathological types.The positive expression of fibulin-5in epithelial ovariancarcinoma was negatively correlated with MVD(P＜0.05),and positivelycorrelated with RI(P＜0.05).Conclusion1Along with the progress of ovarian epithelial tumors, the medianvalues of RI decline, and MVD rise.2There is a negative correlation between the expression of fibulin-5protein and the progression of epithelial ovarian tumors.3The low expression of fibulin-5in epithelial ovarian carcinomas arerelevant with the tumor angiogenesis.