| ObjectiveBy testing pre and post neo-adjuvant chemotherapy, the expressions of PI3K, P-AKT in advanced epithelial ovarian cancer tissue, to investigate whether neo-adjuvant chemotherapy activates drug resistance through PI3K/AKT signal transduction pathway; and analyzed the expression of drug resistance associated genes MRP1 and TopoⅡαbefore and after neo-adjuvant chemotherapy. These indicators predict the feasibility of neo-adjuvant chemotherapy.Methods1. Tissue collectionSpecimens from the First Affiliated Hospital of China Medical University gynecology surgery and pathology confirmed advanced epithelial ovarian cancer were 22 cases. Aged 37-71 years, median age 54 years; FIGO stage:StageⅢin 16 cases, StageⅣin 6 cases from January 2006 to December 2009; Tissue type:serous cystadenocarcinoma in 15 cases, mucinous cystadenocarcinoma in 7 cases; All patients underwent correspondingly preoperative neo-adjuvant chemotherapy (1-3 cycles), then 6-8 cycles of chemotherapy after cytoreductive surgery Chemotherapy for the CP or TP. Postoperative follow-up:to cut-off point,22 patients there were 5 deaths,11 patients survived,6 patients lost to follow. All organizations are formalin-fixed, paraffin-embedded. 2. MethodsImmunohistochemistry SP method in 22 patients with the paraffin-embedded specimens from primary ascites before neo-adjuvant chemotherapy, or ultrasound-guided omental biopsy specimens, and paraffin specimens from surgical resection in ovarian cancer tissue after chemotherapy were paraffin self-control study. Paraffin-embedded tissues for PI3K, P-AKT, TopoⅡα, MRP1 are labeled, antibody working concentration is 1:200, concrete steps can be operated in strict accordance with manual norms of SP immunohistochemistry kit, and at the same time with a blank, negative control.3. Statistical AnalysisResults of application of SPSS13.0 statistical software analysis system. Grade data using paired Wilcoxon signed-rank test and test and grade data correlation analysis using logistic regression, the survival rate is estimated using Kaplan-Meier method was used to compare survival rates between the two groups log-rank test. Hypothesis testing the significance level P<0.05 statistically significant.Results1. After neo-adjuvant chemotherapy in ovarian cancer tissue, the expression level of PI3K protein were significantly lower than before chemotherapy, the difference between the two groups was significant (P<0.05).2. After neo-adjuvant chemotherapy in ovarian cancer, P-AKT protein expression was significantly lower than that before chemotherapy, the difference between the two groups was significant (P<0.01).3. Before and after neo-adjuvant chemotherapy, the expression of MRP1 was no significant changes, the result was not statistically significant (P> 0.05).4. After neo-adjuvant chemotherapy compared with before chemotherapy, the expression of TopoⅡαdecreased, the result was statistically significant (P<0.05).but compared the decreased expression of TopoⅡαwith the no changed expression of TopoⅡα, the progression-free survival rate of those was not significant changes (P> 0.05).5. The progression-free survival rate of non-resistant group before chemotherapy was significantly higher than resistance group, the differences between the two groups was statistically significant (P<0.05).6. In advanced epithelial ovarian cancer P-AKT and PI3K expression with MRP1 expression exists correlation (r=0.685,0.634, both P<0.05).Conclusions1. PI3K and P-AKT expression after chemotherapy were lower than before chemotherapy. Shows that after neo-adjuvant chemotherapy PI3K/AKT signal transduction pathway did not appear to unusual activated, and short courses of chemotherapy can not be inferred to generate significant resistance.2. The expression of TopoⅡαafter chemotherapy compared with chemotherapy decreased, but progression-free survival of decreased expression were not significantly reduced. Shows that after neo-adjuvant chemotherapy, because the changed expression of TopoⅡα, it may lead to the resistance to chemotherapy.3. Before chemotherapy progression-free survival of non-resistant group was significantly higher than resistance group. Therefore, before chemotherapy, MRP1 or TopoⅡαis a prompt detection of drug resistance, then be careful of neo-adjuvant chemotherapy.4. PI3K and P-AKT expression in ovarian cancer were correlated with the MRP1, suggesting that abnormal activation of PI3K/AKT pathway may be one of the mechanisms of drug resistance of ovarian cancer.
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