The Expression And Significance Of Syndecan-1and EMMPRIN In Epithelial Ovarian Tumor

Objective：Ovarian carcinoma is one of the three malignant tumors infemale reproductive system and is responsible for more deaths than any othergynecologic cancer. No means of early detection for ovarian carcinoma hasbeen discovered; consequently, about two-thirds of patients are diagnosed atadvanced tumor stage. The overall5-year survival rate of ovarian carcinoma isless than30％. With the rapid development of operation, chemotherapy andradiotherapy in ovarian germ cell tumors, its5-year survival rate has beenimproved. However, due to the high recurrence rate after surgery of ovarianepithelial carcinoma, the rate of survivors has not changed. Direct spread andperitoneal implants are major transfer pathways of malignant ovarian tumor,but until now the mechanism is unclear. Therefore, it is necessary to find outthe correlative factors of invasion and metastasis, in order to diagnose theepithelial ovarian tumors in earlier time. Syndecan-1is the member of heparinsulfate proteoglycans(HSPGs), which participate in several cell regulationprocesses through cell-cell adhesion, cell-extracellular matrix adhesion,migration and morphogenesis. Reduced Syndecan-1expression, measured byIHC, has been related to the growth and migration of tumor cells. EMMPRINis the member of IgSF, its can stimulate the fibroblasts to secrete MMP, whichcan degradate the basement membrane and extracellular matrix. It was shownthat this function of EMMPRIN can promote tumor invasion and metastasis.We investigate the expression of Syndecan-1mRNA and protein, EMMPRINmRNA and protein in epithelial ovarian cancer, borderline ovarian tumor andbenign ovarian tumor by immunohistochemistry and RT-PCR. The relationwas analyzed among the protein and mRNA expression with histologicalclassification, cell differentiation, FIGO stage. We hope the results of ourresearch can provide experimental basis for the diagnosis of epithelial ovarian tumor.Methods:1The choice of specimen: We selected specimens of epithelial ovariantumor from The Four hospital, Hebei Medical University. All specimens werestored immediately by liquid nitrogen and10%formalin fixed. The specimenswere all confirmed by pathology. There are46cases epithelial ovarian cancer,20cases borderline ovarian cystadenoma and17cases benign ovariancystadenoma. All the cases of epithelial ovarian tumor was not treated byanti-cancer therapy.2The specimens by10%formalin fixed were embedded by paraffin. Allof them were made into4um slices. Immunohistochemistry was used to detectthe expression status of Syndecan-1and EMMPRIN protein in epithelialovarian cancer, borderline ovarian cystadenoma and benign ovariancystadenoma. Expression of Syndecan-1mRNA and EMMPRIN mRNA weredetermined by reverse transcriptase polymerase chain reaction (RT-PCR).3Statistics: After data were collected, SPSS13.0was applied to analyzethe results of experiment. We can analyze the expression difference of the twokinds of proteins and mRNA by the statistics. Meanwhile, we will alsoresearch the relationship with epithelial ovarian cancer clinicopathologicalparameters.Result:1The results showed the positive expression rate of Syndecan-1inbenign ovarian cystadenoma, borderline ovarian cystadenoma, and epithelialovarian cancer were82.35％,65％and39.13％. The expression ofSyndecan-1mRNA in benign ovarian cystadenoma was1.25±0.22. In theborderline ovarian cystadenoma, the Syndecan-1expression was1.08±0.21.However, the expression of syndecan-1mRNA in epithelial ovarian cancerwas0.91±0.24. The difference between benign ovarian cystadenoma andepithelial ovarian cancer was significant. There was no difference betweenbenign ovarian cystadenoma and borderline ovarian cystadenoma, borderlineovarian cystadenoma and ovarian cancer.(P＞0.05) 2For ovarian benign tumor tissue, positive staining of EMMPRINprotein occupied29.41％(5/17), and the positive expression rate ofEMMPRIN in borderline ovarian cystadenoma was35％(7/20). The positiveexpression rate of EMMPRIN in epithelial ovarian cancer was80.43％(37/46).In the ovarian benign tumor, the expression of EMMPRIN mRNA was0.45±0.26. The expression of EMMPRIN mRNA in borderline ovariancystadenoma was1.10±0.21. The expression of EMMPRIN mRNA inepithelial ovarian cancer was1.35±0.23. There was obvious differencebetween ovarian benign tumor and epithelial ovarian cancer, borderlineovarian cystadenoma and epithelial ovarian cancer. EMMPRIN geneexpression was no obvious difference between ovarian benign tumor andborderline ovarian cystadenoma.(P＞0.05)3We analyzed the Syndecan-1positive expression and the expression ofSyndecan-1mRNA in epithelial ovarian cancer classified by histological gradeand clinical stage. The expression of high differentiation was obvious higherthan that of low differentiation. The difference was significant (P＞0.05). Thedifference between high differentiation and moderate differentiation was notsignificant. The difference between moderate differentiation and lowdifferentiation was not significant (P＞0.05). The expression of Syndecan-1mRNA and protein in the first stage+secondary stage was significantly higherthan the tertiary+fourth stage (P＜0.05). The expression of Syndecan-1mRNA and protein has nothing to do with tumor pathological type (P＞0.05),but has significant correlation with clinical stage and tissue differentiation.4We also analyzed the EMMPRIN positive expression and EMMPRINmRNA expression in epithelial ovarian cancer classified by histological gradeand clinical stage. The expression of high differentiation was obvious higherthan that of low differentiation. The difference was significant (P＜0.05). Thedifference between high differentiation and moderate differentiation was notsignificant. The difference between moderate differentiation and lowdifferentiation was not significant (P＞0.05). The expression of EMMPRINmRNA and protein in the first+secondary stage was significantly higher than the tertiary+fourth stage (P＜0.05). The expression of EMMPRIN mRNAand protein has significant correlation with clinical stage and tissuedifferentiation, but has nothing to do with tumor pathological type (P＞0.05).Conclusion:1The positive rate of Syndecan-1protein and expression of mRNA inovarian benign tumor were obviously higher than that of the borderline tumorand epithelial ovarian cancer. With the increase of the level of malignant, thepositive rate and expression level get decrease. We hypothesized that the downregulation of syndecan-1plays an important role in the processes of epithelialovarian cancer. However, in the ovarian benign tumor the expression ofEMMPRIN mRNA and the positive rate of EMMPRIN protein were obviouslylower than that of the borderline tumor and epithelial ovarian cancer. With theincrease of the level of malignant, the expression of positive rate and mRNAquantity increased gradually. The results suggest that the express hypertensionmay promote the occurrence and development of tumor.2In the high differentiation and moderate differentiation group, theexpression of Syndecan-1mRNA and protein were higher than that in the lowdifferentiation group. With the increase of clinical stage, the expression ofSyndecan-1positive rate and the level of mRNA get lower. However, theexpression of EMMPRIN mRNA and protein in the high differentiation andmoderate differentiation group was lower than that in the low differentiationgroup. The expression of EMMPRIN mRNA and protein get much higher withthe increase of the clinical stage. The expression of Syndecan-1andEMMPRIN in the ovarian tumor has nothing to do with tumor pathologicaltypes.3The expression of Syndecan-1mRNA and protein were inverselyrelated to the expression of EMMPRIN mRNA and protein in the epithelialovarian cancer. We speculated that the low expression of Syndecan-1and highexpression of EMMPRIN has relevance with the occurrence and developmentof epithelial ovarian tumor.