P-Glycoprotein in Human Primary Ovarian Cancer Expression of Multidrug Resistance Gene and Localization of Updated Version

Resistance to chemotherapy is the major obstacle to controlling malig nant tumors. To characterize multidrug resistance phenotype in human primary ovarian cancer without chemotherapy, expressions of the inilrl gene in 52 cases of ovarian cancer (44 common epithelial, 5 nonepithelial, and 3 metastatic cancers) were analyzed by polymerase chain reaction of RNA after reverse transcription. Furthermore, localization of P-glycoprotein, which is encoded by the mdrl gene, was studied immunohistochemically. Although overall expression of the nutrìgene was relatively low, its expression level was the highest in well-differentiated cancer tissues. Se rous and mucinous adenocarcinomas showed higher levels of expression compared with clear cell and endometrioid carcinomas. P-glycoprotein was positive on luminal surfaces of lining cells of ovarian cancer and on those of inclusion cysts from which epithelial ovarian cancer is considered to develop. Thus, some ovarian cancer cases before chemotherapy are intrinsically multidrug resistant, which can be determined by ¡mirigene expression, and this phenotype should be taken into account for effective chemotherapy of ovarian epithelial carcinomas. adopted to determine expression of the mdrl gene were less sensitive and rather qualitative compared with RT-PCR (10). Despite the fact that about 80% of ovarian cancers arise from a common embryonal precursor, the coelomic epithelium, they are histologically classified into several subtypes according to their differ entiation, and we have demonstrated that c-myc oncogene overexpression in serous adenocarcinoma, which resembles fallopian tube mucosa, is significant (11). In the mouse secretory epithelium of the uterus, which is a normal counterpart of endometrioid carcinoma, mdr gene expression increases dramatically during pregnancy (12). These suggest that certain subtypes of ovarian cancer could be intrinsically chemoresistant. Consequently, we thought it valuable to assess MDR of primary ovarian cancer without chemotherapy according to histo lÃ3gica!differentiation. In the present study, we analyzed mdrl gene expression by RT-PCR and P-gp production by immunohistochemistry in ovarian cancer tissues.