The Expressions And Clinical Significance Of The P53, P21^waf1, Cdk1 Proteins In Epithelial Ovarian Cancer

Background:Ovarian cancer (OC) is one of the three kinds of malignant carcinoma in female genital system, incidences 4% in the female malignant carcinoma, and it also is the leading cause of death from gynecologic cancers. Though the death rate of OC is improved with the development of operation and chemical therapies, its biological mechanism is still unclear. The dysregulation of the cell cycle is closely correlated to the tumorigenesis and progression, cell DNA is hazarded by the exogenous and endogenous factors endlessly in the cell cycle proceeding.The DNA damaged checkpoints are activated while the DNA is damaged, to activate the repair mechanism, to restore the damaged DNA before the mitosis and ensure the integrality of the genomics.If the restorations fail or the damages accumulate,there would be tumorigenesis caused by uncontrollable cell proliferationP53, P21^WAF1 and CDK1 are the core factors of the p53 pathway of the G2/M checkpoint in the cell cycle, P53 affects CDK1 mainly through P21^WAF1 to regulate G2/M checkpoint. So far, many researches indicate that the factors participate the G2/M checkpoint are closely correlated to the OC, their expressions and dysregulation are related to the origination and progression of the OC. Nowadays the studies to the epithelial ovarian cancer in domestic and oversea are mainly localized at the tumor-inhibition genes and tumor proteins regulation, seldom localized at G2/M checkpoint. This study detected the expression of P53, P21^WAF1 and CDK1 proteins in the p53 pathway of the G2/M checkpoint in 20 normal ovaries, 20 patients with benign epithelial cancer and 76 patients with ovarian carcinoma, then analyzed their correlations and the relations between their expressions and the clinicopathological features, to identify the functions of the key factors in the p53 pathway in epithelial ovarian cancer, to investigate the functions of the p53 pathway in epithelial ovarian cancer and to furtherly comprehend the molecular biology mechanism of the epithelial ovarian cancer.ObjectiveThis study used immunohistochemistry to detect the expressions of P53, P21^WAF1 and CDK1 proteins in normal ovaries, benign epithelial cancer and epithelial ovarian cancer, to analyze their correlations and the relations between their expressions and the clinicopathological features, to identify the functions of the key factors in the p53 pathway in epithelial ovarian cancer, to investigate the functions of the p53 pathway in epithelial ovarian cancer, further to get more messages of the biological mechanism of the EOC and to furtherly comprehend the molecular biology mechanism of the epithelial ovarian cancer.Method1. Immunohistochemistry was used to detect the expressions of P53, P21^WAF1 and CDK1 proteins in the p53 pathway of the G2/M checkpoint in 20 normal ovaries, 20 patients with benign epithelial tumor and 76 patients with epithelial ovarian cancer, analyzed the correlations among these factors and the relations between their expressions and the clinicopathological features.2. Statistical analysis: the SPSS statistical package program 13.0 was used for all analysises. Associations of P53, P21^WAF1 and CDK1 expressions in different ovarian tissues were tested by Chi-square Test, the correlations of P53, P21^WAF1 and CDK1 expressions in the epithelial ovarian cancer were tested by Spearman Correlation test. Results1. The expressions of P53 protein in normal ovary, benign epithelial tumor and epithelial ovarian cancer are 0%(0/20), 0%(0/20) and 60.5%(46/76) respectively, there is no statistical difference between normal ovarian and benign epithelial tumor (P>0.05) .The expression in EOC is obviously higher than these in normal ovarian and benign epithelial tumor, there are statistical differences(P<0.05).2. The expressions of P21^WAF1 protein in normal ovary, benign epithelial tumor and epithelial ovarian cancer are 90.0%(18/20), 65.0%(13/20) and 36.8%(28/76) respectively, there is no statistical difference between normal ovarian and benign epithelial tumor (P>0.05).The expression in EOC is obviously lower than these in normal ovarian and benign epithelial tumor, there are statistical differences (P<0.05).3. The expressions of CDK1 protein in normal ovary, benign epithelial tumor and epithelial ovarian cancer are 20%(4/20), 40%(8/20) and 92.1%(70/76) respectively, there is no statistical difference between normal ovarian and benign epithelial tumor (P>0.05).The expression in EOC is obviously higher than these in normal ovarian and benign epithelial tumor, there are statistical differences(P<0.05).4. The correlations of P53, P21^WAF1 and CDK1 proteins in EOC: there is negative correlation between P53 and P21^WAF1 proteins(r=-0.388, P=0.001); there is positive correlation between P53 and CDK1 proteins(r=0.263,P=0.022); there is negative correlation between P21^WAF1 and CDK1 proteins(r=-0.282,P=0.014).5. The expressions of P53 protein in EOC are 33.3%(8/24) and 73.1%(38/52) inI / II and III/IV stage EOC, there is statistical difference(P<0.05); the expressions of P53 protein are 28.6%(4/14), 59.1%(13/22) and 72.5%(29/40) in G1,G2 and G3 grade EOC, there is statistical difference(P<0.05),the expression of P53 protein is significantly associated with the FIGO staging and histology grade. The expressions of P21^WAF1 protein in EOC are 58.3%(14/24) and 26.9%(14/52) inI /II and III/IV stage EOC, there is statistical difference(P<0.05), the expression of P21^WAF1 is significantly associated with the FIGO staging.There is non correlations between the expressions of CDK1 protein and the clinical pathology features of EOC.Conclusions1. Aberrant expressions of P53, P21^WAF1 and CDK1 proteins are involved in the tumorigenesis and progression of epithelial ovarian cancer.2. The p53 pathway of the G2/M checkpoint may be involved in the tumorigenesis and progression of epithelial ovarian cancer.3. P53 protein is associated with the malignancy of epithelial ovarian cancer4. P53 and P21^WAF1 proteins may be involved in the development of epithelial ovarian cancer.5. The detection of CDK1 in different ovarian tissues may be helpful in the diagnosis of epithelial ovarian cancer.