The Expression And Clinical Significance Of The Cyclin Dependent Kinase 1 (cdk1) And Cdc25 Phosphatases B (cdc25b) In Epithelial Ovarian Cancer

BackgroundMalignant ovarian tumors are one of the three kinds of malignant tumors of female genital system,and it is the leading cause of death from gynecologic malignancies.Epithelial ovarian cancer(EOC) is the most common,accounting for 75%～90%of the primary ovarian malignancy.Because of lack of early warning signs and typical symptomatology,metastatic easily and poor prognosis,EOC has become a serious threaten to the lives and health of women.Although CA₁₂₅ is the only confirmed sensitive diagnosis indicator,but it is only applied to monitor the level of relif or deterioration of the patients' condition.Furthermore the relatively specific biomarker used for early diagnosis and prognosis judgement is still not found,so researching the new effective indicator for which,improving the survival rate of patients with ovarian carcinoma,is the most considerable subject of all.Cell growth and proliferation being out of the control is the main characteristic of the malignancy.The abnormal of cell proliferation,differentiation and apoptosis are involved in the tumorigenesis and development,and the disorder of cell cycle regulation mechanism plays an important role in carcinogenesis.Cyclin-dependent kinases(CDKs) are the core molecule of cell cycle regulation mechanism,which with Cyclins,CDKs inhibitor(CKIs) and so on compose the network of cell cycle regulation,contributing cell cycle progression.CDKI plays an important role in G₂/M phase,at the late G₂ phase CDK1 combines with CyclinB1 to form maturation promoting factor(MPF),causing CDK1 molecular conformation changed and exposing Thr14/Tyr15 residues.CDC25B phosphatase dephosphorylate Thr14/Tyr15 residues to activates MPF,promotes the cell cycle progression and cell division.ObjectiveIn this study,Streptavidin-Peroxidase(SP) immunohistochemistry technique was used to detecte the expressions of CDK1 and CDC25B protein in 20 cases normal ovarian tissues,20 cases benign epithelial ovarian tumor tissues and 76 cases epithelial ovarian cancer tissues,then analyze the correlations and relations of their expressions and the clinicopathological features,to identify the roles of CDK1 and CDC25B in the tumorigenesis and development of EOC.Materials and methods1.Collect paraffin imbedding ovarian tissues of 20 hysteromyoma patients and 96 ovarian epithelial tumors,who had pathological and clinical integrity data and underwent gynecological operation at the Department of Gynecology,the First Affiliated Hospital of Zhengzhou University,from November 2004 to September 2007.All the patients didn t get any radiotherapy,chemotherapy and other therapy before operation.Among them,there are 76 epithelial ovarian cancers(include 54 serous cystadenocarcinoma,22 mucinous cystadenocarcinoma),20 ovarian benign ovarian epithelial tumors(10 serous cystadenoma,10 mucinous cystadenoma).2.Streptavidin-Peroxidase(SP) immunohistochemistry technique was used to detecte the expression of CDK1 and CDC25B protein in 76 cases of epithelial ovarian cancer,20 cases of ovarian benign epithelial tumor and 20 cases of normal ovarian tissues,analyze the correlations and relations between their expressions and the clinicopathological features of EOC.3.Statistical analysis:the SPSS statistical package program 13.0 was performed for all analysis.Association of CDK1 and CDC25B expressions in different ovarian tissues were tested by Chi-square Test,the correlation of CDK1 and CDC25B expressions in the epithelial ovarian cancer were tested by Spearman Correlation test. There was a statistical significance when P＜0.05.Results1.CDK1 is mainly localizated in the cytoplasm,the positive rate of CDK1 protein expression in normal ovary,benign ovarian epithelial tumor and epithelial ovarian cancer were 15.0%(3/20),30.0%(6/20)and 86.8%(66/76) respectively;The expression in EOC is significantly higher than that in normal ovary and benign ovarian epithelial tumor(P＜0.05),there is no statistical difference between normal ovary and benign ovarian epithelial tumor(P=0.256).2.The expression of CDK1 protein in EOC wasn't significantly associated with the histological grade,pathological subtype,FIGO stage,age and lymph node metastases(P＞0.05).3.CDC25B is mainly localizated in the nucleus,the positive rate of CDC25B protein expression in normal ovary,benign ovarian epithelial tumor and epithelial ovarian cancer were 0.0%(0/20),20.0%(4/20)and 57.9%(44/76) respectively;The expression in EOC is significantly higher than that in normal ovary and benign ovarian epithelial tumor(P＜0.05),there is no statistical difference between normal ovary and benign ovarian epithelial tumor(P=0.035).4.The expression of CDC25B protein in EOC was significantly associated with the FIGO stage and lymph node metastasis(P＜0.05),and wasn't significantly associated with the histological grade,pathological subtype and age(P＞0.05).The positive rate of CDC25B protein expression in tissues with FIGOⅢ,Ⅳstage was significantly higher than that ofⅠ,Ⅱstage(P＜0.05),there is no statistical difference between FIGOⅠandⅡstage(P=1.000).The positive rate of CDC25B protein expression in tissues with lymphoid node metastasis was significantly higher than that of without lymphoid node metastasis(P＜0.05).5.The correlation between the expression of CDK1 and CDC25B protein in EOC:The positive rate of CDK1 and CDC25B protein co-expression is 56.6% (43/76),the correlation coefficient was 0.378.There was positive correlation between the expression of CDK1 and CDC25B protein in EOC(P＜0.05). Conclusions1.The overexpression of CDK1 protein may contribute to the malignant proliferation of tumor and play an important role in carcinogenesis and progression of epithelial ovarian cancer.2.The overexpression of CDC25B protein may be associated with the carcinogenesis,progression,invasion and metastasis of epithelial ovarian cancer.3.The overexpression of CDK1 and CDC25B protein may have synergistic effect in the carcinogenesis of epithelial ovarian cancer.