Epithelial Ovarian Cancer In The Er, Pr, Ca125, Ki - 67, The Expression Of P53 And Chemotherapy Sensitivity Study

Background and Objective:Ovarian cancer is the third leading cause of death and has the highest mortality rate among the gynecologic malignancies. Paclitaxel/platinum is currently the first-line regimen for postoperative patients with epithelial ovarian cancer (EOC)。 Although the combination chemotherapy including paclitaxel with cisplatin and paclitaxel with carboplatin has improved the prognosis of initial treatment of epithelial ovarian cancer, five-year survival rate of advanced stage rambled between20%-30%. The leading factor of the patients’death with EOC is not sensitive to chemotherapy and recurrence, one of the reasons is primary of acquired drug resistance after chemotherapy.This study was to compare the different expression of ER、PR、CA125、Ki67、 P53and to analysis the correlation between the efficacy of chemotherapy and the expression levels of selected immunohistochemical indicators. We attempted to discover molecular markers to predict response to paclitaxel/platinum in EOCs. Predictors to chemoresistance may be helpful to achieve individualized treatment and to improve clinical outcome.Methods:Retrospectively analyzed the clinical characteristics、treatment and the short-term therapeutic effects of epithelial ovarian cancer patients in Obstetrics&Gynecology Hospital of Fudan University between2003and2008. A total of230patients underwent optimal cytoreductive operation and received regular postoperative chemotherapy was recruited in this study. The Patients’immunohistochemical proteins were reviewed respectively and compared, including ER, PR, CA125, Ki67, and P53. Statistics analysis was performed to study the relationship between these proteinic markers and the chemotherapy efficacy, and to compare the chemotherapy efficacy between the different express of immunohistochemical proteins.Results:Part I:230patients included149serous adenocarcinoma cases and81non-serous adenocarcinoma cases,55.8%patients were postmenopausal.120patients were in FIGO stage Ⅲ/Ⅳ, accounted for52%.24patients had the residual lesions (>2cm), accounted for10.3%.122patients had lymph node metastases, accounted for53.2%.Part II:Pearson Rank Correlation analysis revealed among5molecular markers, ER, PR, CA125and P53protein expression had significant negative associated with chemotherapy sensitivity (P=0.018,0.035,0.007and0.001). There were no significant associated in the expression of Ki-67and chemotherapy sensitivity (P>0.05).Independent-Samples T Test analysis revealed the decreasing of serum CA125levels had significant difference in patients with PR-negative and PR-positive expression (P=0.007), and also in patients with P53-negative and P53-positive expression (P=0.041). Compared with patients with PR-/P53positive, patients with PR-/P53negative were more likely to have the higher extent of the decrease of serum CA125level after optimal cytoreductive surgery and chemotherapy.Part Ⅲ:Multiple regression analysis showed: Y=0.76-0.024X1-0.005X2-0.052X3-0.048X4(P<0.05). From the standardized coefficients, CA125and P53protein expression are important factors, ER and PR protein expression is the secondary factors.Stepwise regression analysis showed:Y=0.757-0.058X’1-0.064X’2(P<0.01). This equation explained there were significant linear relationship in the expression of CA125、P53and chemotherapy sensitivity (P=0.023and0.010).Conclusion:ER、PR、CA125and P53protein expression were related to the chemotherapy sensitivity of the patients with epithelial ovarian cancer. The express of these immunohistochemical proteins were predictive factors in selecting first-line chemotherapy for epithelial ovarian cancer. These molecular markers might have the value in chemotherapy prediction.