The Expressions And Clinical Significance Of HIF-1α,MRP And P-gp In Epithelial Ovarian Cancer

Objective:This study was designed to evaluate the expression of HIF-1α,MRP and P-gp in epithelial ovarian tumor by immunohistochemistry and to investigate the relationships between their expressions and the clinicopathological variables and prognosis respectively and we also analysed the association among their expressions,which may reveal the role of hypoxia in the pathogenesis and progression of ovarian caricinoma.Thus we will find a promising target for therapy and a potentially useful factor for detection the prognosis in ovarian carcinoma,which may retroconverse tumor drug resistance and improve the effect of chemotherapy.Methods:Using immunohistochemistry to evaluate the expression of HIF-1α,MRP and P-gp in ovarian epithelial tumor tissues respectively.Specimens were obtained from the 132 patients who were operated for epithelial ovarian cancer,60 cases of bordline tumor,42 cases of benign ovarian tumor in the Department of Obstetrics and Gynecology of Qilu Hospital,Shandong University from January,1999 to April,2006. The study of associations B7-H4 with clinicopathological variables,clinical remission and prognosis was done.All of the patients' clinical data were complete and the follow-up results of bordline tumor were intact.All the Specimens were diagnosed by HE pathology examination.χ~2 test and Fisher's exact test were used to compare of sample rate,while the ranked data such as factors' positive levels and the associations of variables were tested by Spearman rank correlation analysis,survival analysis were made by using the Kaplan Meier method andχ~2 test was used to evaluate the difference of prognosis, the survival difference between any two groups was analysed by Log Rank test,the relationship between the outbreak age of cervical cancer and the clinical was analysed by cox regression model.Statistical analysis was done using SPSS13.0 software,the differences was statically significant when it is P＜0.05.Results:The positive proportions of HIF-1α,MRP and P-gp in epithelial ovarian carcinoma were significantly higher than benign,borderline tumors(P＜0.001) and the positive levels of the three factors had positive relationships with malignant degree in ovarian carcinoma(P＜0.001).The positive proportion of HIF-1αprotein in endometrioid ovarian carcinoma was significantly higher than serous and mucinous tissues(P=0.030),while the expression of MRP was significantly higher than others (P=0.012).The expression of HIF-1α,MRP and P-gp had correlation with each other(P＜0.001).Patients who have positive expressions of HIF-1αand MRP repectively were characterized by a significantly worse prognosis in term of overall survival than negative ones(P＜0.001).The 3-year survival rate and clinical remission rate were significantly lower in patients who have HIF-1αnegative expression than the positive group(P＜0.001,P=0.013),and MRP has the same result (P＜0.001).There was no correlation between P-gp expression and clinical remission and prognosis.The HIF-1α+/MRP+ group had significantly later clinical stage (P＜0.001),worse grade(P＜0.001),higher level of CA125(P=0.003)and higher lymph node metastases than the HIF-1-/MRP-,HIF-1+/MRP- and HIF-1-/MRP+ groups,while no correlation with the size of residual lesion(P=0.089).The group of HIF-1α+/MRP+ had significant lower clinical remission rate and shorter survival than the groups of HIF-1+/MRP-,HIF-1-/MRP+和HIF-1-/MRP-(P＜0.001).Age and histological type had no correlation with prognosis(P=0.443).cox regression model revealed prognosis of epithelial ovarian carcinoma had positive correlations with HIF-1α,MRP,CA-125,residual lesion,lymph node metastasis,clinical stage and clinical remission. Inclusion:The positive levels of HIF-1α,MRP and P-gp had positive relationships with malignant degree in ovarian carcinoma and the expression of each protein had intimate correlations,which may reveal they had synergistic effect in their expression so as to induce tumor drug resistance.The over expression of HIF-1αand MRP especially both positive in ovarian carcinoma may deteriorate the tumor behavior and cause drug resistance.Detection of HIF-1αin combination with MRP will provide a promising method to evaluate the effect of chemical therapy and prognosis estimation in ovarian carcinoma.