A Study On The Expression Of P-gp ,GST-πand Topo-Ⅱ Proteins In Primary Epithelial Ovarian Cancer And Their Relationship With ATP-tumor Chemosensitivity Assay

Objecitive:(1)To investigate the expression of drug resistance-associated proteins P-gp,GST-Ï€ and Topo-â…¡ in primary epithelial ovarian cancer (PEOC) and their clinical significance. (2)To explore the feasibility of the ATP-tumor chemosensitivity assay(ATP-TCA)applied in chemotherapy of PEOC.(3)To evaluate ex vivo sensitive rate of specimens of fresh ovarian cancer to five cytotoxic drugs.(4)To analyse the relationship between the three drug resistance-associated proteins and ATP-TCA.Methods:Expressions of P-gp ,GST-Ï€and Topo-â…¡proteins were examined in paraffin sections from 53 resected specimens of PEOC patients and 10 normal ovarian tissues of other patients by S-P immunohistochemical staining. ATP-TCA was used to detect the sensitive rate of 24 specimens of fresh ovarian cancer to five cytotoxic drugs as follows: paclitaxel(TAX),gemcitabine(GEM), doxorubicin(ADM),topotecan (TPT), cisplatin(DDP).Results:â‘ ,In 10 normal ovarian tissues,none of P-gp and GST-Ï€proteins expressions was observed,the expression rate of Topo-â…¡proteins was 70%.In 53 epithelial ovarian cancer tissues,the expression rates of P-gp,GST-Ï€ and Topo-â…¡proteins were 47.2%(25/53),56.6%(30/53), 62.3%(33/53) respectively. The co-expression rate of P-gp and Topo-â…¡proteins was 20.7%(11/53), of P-gp and GST-Ï€ proteins was 26.4%(14/53),of GST-pi and Topo-â…¡proteins was 32.1%(17/53) , of P-gp,GST-Ï€ and Topo-â…¡proteins was 15.1%(8/53).â‘¡,Expressions of P-gp,GST-Ï€and Topo-â…¡proteins were associated with histologic subtypes respectively: the expression of P-gp and GST-Ï€proteins in mucinous tumors was obviously more than that in serous and endometrioid ones, P?<0.05;mucinous tumors showed sharply decreased Topo-â…¡protein expression compared with serous and endometrioid ones,P<0.05.But all of them had no statistical correlation with other clinicopathological parameters, such as clinical stage, tumor grade or residual tumors , P > 0.05.â‘¢,Evaluable test results were achieved in 23 of 24 specimens, the evaluability rate of ATP-TCA was 95.83%. The ex vivo sensitive rate of TAX was 91.30% (21/23),of GEM was 86.96%(20/23) ,of ADM was 65.22%(15/23),of TPT was 47.83%(11/23),of DDP was 21.74%(5/23)sequently. â‘£,The expression of GST-Ï€protein was concordant with the resistance to cisplatin(P=0.037),but not with that to TAX,GEM,ADM and TPT. the expression of P-gp and Topo-â…¡proteins was not associated with any resistance to DDP,ADM,TAX,GEM,TPT.Conclusion:â‘ ,The expression rates of P-gp,GST-Ï€ and Topo-â…¡proteins were high and all of them were associated with histological sub-types in PEOC.It was suggested that there was a phenomenon of intristic multidrug resistance in PEOC.â‘¡,ATP-TCA was a sensitive,reliable and standardization method for tumor chemosensitivity testing, it deserved to study further for screening anticancer agents in chemotherapy of ovarian cancer.â‘¢,The ex vivo sensitive rates of paclitaxel and gemcitabine were high irrespective of expression of the three drug resistance-associated proteins,which indicated that they could be applied in recurrent ovarian carcinoma patients and refractory ones.â‘£,The positive expression of GST-Ï€protein might be correlated with the resistance to cisplatin in PEOC.Furter clinical studies in a large group of patients were needed for comfirmation whether GST-Ï€protein expression could become a useful marker to predict the resistance in epithelial ovarian cancer patients.