Association Between TGFBI Promoter Methylation And CyclinD1Protein Expression In Epithelial Ovarian Carcinomas Tissues

The incidence of ovarian carcinomas ranked third of gynecological tumors and it is one of the malignant diseases which mortality rate ranked first. This is because ovarian anatomical location is deep in pelvic cavity, most of the patients have no symptoms early, so it is difficult to find in early stage and give the effective treatment. About60%-70%of patients with ovarian carcinoma are diagnosed in clinically advanced stages. Nearly half a century, ovarian carcinomas research has been the difficulty and hot spot in the study of gynecological tumors. After the efforts of the world experts and researchers, they have improved operation skills and have found the new chemotherapy drugs and designed more and better the chemotherapy methods. Although it have improved the recent life quality of the late ovarian malignant tumor patients, but5years survival is still hovering25%to35%. So ovarian carcinomas have become the main threat to women’s life, and92%of ovarian carcinomas originated in the epithelial ovarian tissue. At present epithelial ovarian carcinomas etiology and pathogenesis is still not quite sure, yet the lack of effective early diagnostic methods, the study of occurrence and pathogenesis of ovarian carcinoma has immense importance in the diagnosis and treatment of ovarian carcinoma.TGFBI gene is an important tumor suppressor gene inactived by promoter methylation which is closely related with gynecological tumors. TGFBI promoter methylation was detected by Methylation Specific Polymerase chain Reaction (MSP) in30cases of epithelial ovarian carcinomas tissues and20cases of normal epithelial ovarian tissues and20cases of benign epithelial ovarian tissues; the expression of CyclinDl protein was detected by immunohistochemistry.Then analysis their correlations. In order to get the mechanism of TGFBI gene methylation and CyclinDl high expression in epithelial ovarian carcinomas and find new targets for epithelial ovarian carcinomas.ObjectiveTo investigate TGFBI promoter methylation and its possible correlation with the expression of CyclinDl protein in epithelial ovarian carcinomas tissues, and to evaluate the effect of TGFBI promoter methylation action on the development of epithelial ovarian carcinomas.Materials and Methods1. Study Object:70cases of epithelial ovarian tissues fixed in wax were collected from the pathology department of The Third Affiliated Hospital of Zhengzhou University in August2008-March2011. It contains20cases of normal epithelial ovarian tissues in group A,20cases of benign epithelial ovarian tumor tissues in group B and30cases of epithelial ovarian carcinomas tissues in group C (21cases of serous capsule adenocarcinoma,9cases of mucinous capsule adenocarcinoma). The patient’s age ranged from18to70years, the median age is49years. All patients had not received chemotherapy and radiation before.20cases of normal epithelial ovarian tissues were moved out from the normal side of uterus and double accessories.2. Methods:The expression of CyclinDl protein was detected by immunohistochemistry in normal, benign and malignant epithelial ovarian tissues.TGFBI promoter methylation was detected by MS-PCR (methylation specific polymerase chain reaction) in normal, benign and malignant epithelial ovarian tissues. 3. Statistical method:Statistical analysis was done using SPSS17.0. All immunohistochemical data is expressed as mean±standard deviation to analyze their normality and homogeneity of variance respectively. Chi-square test is used to analyze the methylation results, Spearman rank correlation coefficient of the correlation analysis, significant level being0.05.Results1. CyclinDl protein expressed in normal epithelial ovarian tissues is101.98±5.80, in benign epithelial ovarian tissues is118.06±5.89and in epithelial ovarian carcinomas tissues is137.62±7.17.There was a significant increment in epithelial ovarian carcinomas tissues than in benign epithelial ovarian tissues and there was significant increment in benign epithelial ovarian tissues than in normal epithelial ovarian tissues (<0.0167).2. The rate of TGFBI methylation in the benign epithelial ovarian tissues is10.5%and in epithelial ovarian carcinomas tissues is70%. So there was significant increment in the epithelial ovarian carcinomas tissues than in benign epithelial ovarian tissues (P<0.05).3. TGFBI methylation was found in21epithelial ovarian carcinomas tissues; out of which16cases had positive expression of CyclinDl (76.2%). TGFBI unmethylation was found in9epithelial ovarian carcinomas tissues; out of which2cases had positive expression of CyclinDl (22.2%). Higher expression of CyclinDl protein is closely correlated to TGFBI promoter methylation(r=0.505, P<0.05).Conclusions1. TGFBI gene DNA promoter region methylation status was found in epithelial ovarian carcinomas tissues, it plays an important role in the development of epithelial ovarian carcinoma.2. High expression of CyclinDl protein which participate in the occurrence of epithelial ovarian carcinomas. 3. Higher expression of CyclinD1protein is closely correlated with TGFBI promoter methylation. After TGFBI gene was inhibited, CyclinD1protein expression increased; this mechanism may play an important role in the development of epithelial ovarian carcinoma.