The Expression Of P53、livin、ERCC1、BRCA1、PARP In Epithelial Ovarian Cancer And Its Influence To Drug Resistance And Prognosis

Objective: Ovarian cancer is one of the most common malignant tumor of female reproductive system.Its main clinical treatments are surgery and chemotherapy,its 5-year survival rate is about 30%.Drug resistance is one of the most serious challenge in the treatment of ovarian cancer at present. Studying the related genes of drug resistance and prognosis contributes the formulate of ovarian cancer patients’ chemotherapy regimen. In the past studies, BRCA1 、 PARP 、 ERCC1 、 P53 and Livin are related to drug resistance.Our study is to explore the relationship between expression of these genes and drug resistance by immunohistochemistry.We can overcome the drug resistance of ovarian cancer by targeted therapy.It will be a new way for the treatment of ovarian cancer.Methods:1 Selecting 66 cases of epithelial ovarian cancer patients’ paraffin and medical information as study group,all of whom inpatiented in the Fourth Affiliated Hospital of Hebei Medical University from January 2007 to December 2009 and had received staging surgery or cytoreductive surgery and the following standard platinum-based chemotherapy.2 Follow up these cases to find out the time of tumor recurrence and the overall survival.There were 49 patients in drug-resistance group and 17 patients in drug-sensitive group。3 Detects the expression of P53、Livin、ERCC1、BRCA1、PARP in epithelial ovarian cancer by immunohistochemistry.4 All of the dates were analyzed by SPSS 13.0 software wrap.Compared the expression of these genes between drug-resistance group and drug-sensitive group by Chi-square test and Rank sum test. Studied the influence of age,degree of differentiation,clinical stage,the number of preoperative CA125,and the expression of these genes to the overall survival.Used a=0.05 as the test standard,there was significant difference when P<0.05.Results:1 The positive expression rate of P53 in epithelial ovarian cancer was 54.55%(36/66),the positive expression rate of drug-resistance group and drug-sensitive group was 76.47%,46.94% respectively,there was statistically significant difference between them(P<0.05).The positive expression rate of advanced stage(FIGO Ⅲ-Ⅳ) was 63.27%,was 31.25% in early stage(FIGO Ⅰ- Ⅱ).There was statistically significant difference between them(P<0.05).There was no statistically significant difference between different degree of differentiation(P>0.05). The expression of P53 can’t influence the overall survival.2 The positive expression rate of Livin in the cytoplasm of epithelial ovarian cancer was 69.70%,the positive expression rate of drug-resistance group and drug-sensitive group was 61.22%,94.12% respectively,there was statistically significant difference between them(P<0.05).The positive expression rate of advanced stage(FIGO Ⅲ-Ⅳ) was 81.63%,was 31.25% in early stage(FIGO Ⅰ- Ⅱ).There was statistically significant difference between them(P<0.05).There was no statistically significant difference between different degree of differentiation(P>0.05).The expression of Livin can influence the overall survival(P<0.05).3 The positive expression rate of ERCC1 in the nucleus of epithelial ovarian cancer was 51.52%( 34/66),the positive expression rate of drug-sensitive group and drug-resistance group was 38.78%,94.12% respectively,there was statistically significant difference between them(P<0.05).The positive expression rate of poor differentiation and high,moderate differentiation was 69.23%( 18/26), 42.50%( 17/40)respectively.The positive expression rate of advanced stage(FIGO Ⅲ-Ⅳ) was 81.63%,was 31.25% in early stage(FIGO Ⅰ- Ⅱ).There was statistically significant difference between them(P<0.05).The expression of ERCC1 can influence the overall survival(P<0.05).4 The positive expression rate of BRCA1 in the nucleus of epithelial ovarian cancer was 37.88%( 25/66),the positive expression rate of drug-sensitive group and drug-resistance group was 24.49%,76.47% respectively,there was statistically significant difference between them(P<0.05).The positive expression rate of poor differentiation and high,moderate differentiation was 23.08%( 6/26), 47.50%( 19/40) respectively.The positive expression rate of advanced stage(FIGO Ⅲ-Ⅳ) was 44.90%(22/49),was 12.50%(2/16) in early stage(FIGO Ⅰ- Ⅱ).There was statistically significant difference between them(P<0.05).The expression of BRCA1 can influence the overall survival(P<0.05).5 The positive expression of BRCA1 was mainly in the nucleus. The cases of negative group,weak positive group,positive group was 22,25,19 respectively. In the drug-sensitive group, the cases of negative group,weak positive group,positive group was 20,17,12 respectively; In the drug-resistance group, the cases of negative group,weak positive group,positive group was 2,8,7 respectively.There was statistically significant difference between two groups(P<0.05).There was no statistically significant difference between different degree of differentiation and different clinical stage(P>0.05). The expression of PARP can’t influence the overall survival.But if we regard weak positive group and positive group as positive group,the overall survival had statistically significant difference between two groups(P<0.05).6 The expression of PARP correlated positively with the expression of P53,Livin,BRCA1,ERCC1 by Spearman correlation analysis. The expression of P53 correlated positively with the expression of PARP,Livin.The expression of Livin correlated positively with the expression of PARP,P53,ERCC1 by Spearman correlation analysis. The expression of BRCA1 correlated positively with the expression of PARP. The expression of ERCC1 correlated positively with the expression of PARP,Livin.7 The 66 cases of epithelial ovarian cancer patients, all of whom had received staging surgery or cytoreductive surgery and the following standard platinum-based chemotherapy,the overall survivals were 3months to 94 months,the median survival was 68.4 months.The 1-year survival rate,3-year survival rate,5-year survival rate were 95.5%,66.7%,51% respectively.8 The clinical stage can influence the overall survival(P<0.05).The age,degree of differentiation,the number of preoperative CA125 can’t influence the overall survival.The chemotherapy sensitivity rate hadn’t statistically significant difference between different clinical stages and different degree of differentiation(P>0.05).9 Among the influences of age,degree of differentiation,clinical stage,the number of preoperative CA125,chemotherapy sensitivity rate to the overall survival, clinical stage and chemotherapy sensitivity rate were the most important factors.Conclusions:1 The expression of P53,Livin,ERCC1,BRCA1 and PARP could influence the chemotherapy sensitivity rate. The expression of P53,Livin,ERCC1 and BRCA1 in different clinical stags had statistically significant difference.The expression of ERCC1 and BRCA1 in different degrees of differentiation had statistically significant difference.The expression of Livin,ERCC1 and BRCA1 could influence the overall survival.2 The expression of PARP correlated positively with the expression of P53, Livin, BRCA1, ERCC1 by Spearman correlation analysis. The expression of P53 correlated positively with the expression of PARP,Livin.The expression of Livin correlated positively with the expression of PARP,P53,ERCC1 by Spearman correlation analysis. The expression of BRCA1 correlated positively with the expression of PARP,ERCC1. The expression of ERCC1 correlated positively with the expression of PARP、Livin.3 After staging surgery or cytoreductive surgery and the following standard platinum-based chemotherapy,the overall survivals of epithelial ovarian cancer patients were 3months to 94 months,the median survival was 68.4 months.The 1-year survival rate,3-year survival rate and 5-year survival rate were 95.5%,66.7%,51% respectively. The clinical stage can influence the overall survival(P<0.05).The age,degree of differentiation,the number of preoperative CA125 can’t influence the overall survival. Among the influences of age,degree of differentiation,clinical stage,the number of preoperative CA125,chemotherapy sensitivity rate to the overall survival, clinical stage and chemotherapy sensitivity rate were the most important factors.