title: Multidrug resistance-associated biomarkers PGP, GST-pi, Topo-II and LRP as prognostic factors in primary ovarian carcinoma.
abstract: This study aims to investigate the expression of P-glycoprotein (PGP), glutathione S-transferase pi (GST-pi), DNA topoisomerase II (Topo-II) and lung resistance-related protein (LRP) in ovarian carcinoma, thus providing better chemotherapy choice and post-operative prognosis for ovarian carcinoma patients. A total of 80 primary ovarian carcinoma, 16 benign ovarian epithelial neoplasm, and 12 normal ovarian tissue samples were collected. Immunohistochemistry was used to detect the expression of PGP, GST-pi, Topo-II and LRP, and the results were analysed by correlation with clinicopathological parameters. Positive expression rates of PGP, GST-pi, Topo-II and LRP in patients with ovarian carcinoma (57.5%, 58.8%, 76.3% and 73.8%, respectively) were all higher than those found in normal and benign tissue (P<0.05). In clinical stages I/II vs. III/IV, the expression rates of PGP, GST-pi, Topo-II and LRP were 40.7% vs. 66% (P<0.05), 40.7% vs. 67.9% (P<0.05), 66.7% vs. 81.1% (P>0.05) and 55.6% vs. 83.0% (P<0.05), respectively. Carcinoma differentiation ranged from well to poor, and expression levels of each marker were as follows: PGP, 57.9%, 62.1% and 53.1% (P>0.05); GST-pi, 36.8%, 55.2% and 75.0% (P<0.05); Topo-II, 52.6%, 79.3% and 87.5% (P<0.05); and LRP, 84.2%, 69.0% and 71.9% (P>0.05). Ovarian carcinoma patients with PGP-, GST-pi-, Topo-II- and LRP-positive expression had a shorter median survival time than those who were negative for these markers (PGP: 36 months vs. 48 months [P=0.0017]; GST-pi: 36 months vs. 41 months [P=0.0103]; Topo-II: 37 months vs. 39 months [P=0.3811]; LRP: 37 months vs. 55 months [P=0.002]). COX regression analysis demonstrated that the clinical stage of the tumour, and the expression of PGP, GST-pi or LRP, may influence patient survival time after surgery. The relative death risk for patients with clinical stage III/IV tumours increased 9.46-fold compared to those with stage I/II tumours. The relative death risk in the PGP-, GST-pi- and LRP-positive groups increased by 2.049-, 2.452- or 2.609-fold, respectively, compared with the corresponding negative groups. PGP, GST-pi, Topo-II and LRP are all expressed in primary ovarian carcinoma, indicating the presence of multidrug resistance in this disease. Combined evaluation of PGP, GST-pi, Topo-II and LRP expression may enable better chemotherapeutic choice and provide an accurate prognosis for ovarian carcinoma patients.
authors.affiliation: Department of Obstetrics and Gynaecology, Clinical College, Yangzhou University, Yangzhou, P. R. China. ludan1968@yahoo.com.cn
authors.forename: D
authors.initials: D
authors.lastname: Lu
authors.forename: H-C
authors.initials: HC
authors.lastname: Shi
authors.forename: Z-X
authors.initials: ZX
authors.lastname: Wang
authors.forename: X-W
authors.initials: XW
authors.lastname: Gu
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zeng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism; D055815:Young Adult; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D051549:Glutathione S-Transferase pi; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein