RNA expression of MDR1/P-glycoprotein, DNA-topoisomerase I, and MRP2 in ovarian carcinoma patients: correlation with chemotherapeutic response.
OBJECTIVE
Clinical drug resistance is the major obstacle in the successful treatment of ovarian cancer. Besides elevated expression of adenosine triphosphate binding cassette (ABC) transporters, such as MDR1/P-gp or MRP2/cMOAT/ABCC2, alterations in the expression of DNA topoisomerase I (TOP1) are associated with drug-resistant phenotypes in various model systems.


METHODS
In ovarian specimens of 61 patients, the mRNA expression levels of MDR1/P-gp, MRP2, and TOP1 were determined using a competitive quantitative RT-PCR protocol with internal standards. The mRNA expression levels were correlated with the clinical outcome and histopathological criteria. The tumor specimens included 11/61 (18%) benign ovarian tumors, including 2 LMP tumors, and 50/61 (82%) ovarian carcinomas, including 34 primary and 16 recurrent cancers. Moreover, 20/61 (33%) ovarian specimens showed low or no MDR1/P-gp expression.


RESULTS
None of the benign tumors showed MRP2 expression, whereas 15/50 (30%) ovarian carcinomas expressed MRP2. In 61/61 (100%) of the samples, expression of TOP1 could be measured. In patients with recurrent ovarian cancer, no differences in expression of any of the factors could be observed. In patients with primary FIGO III carcinomas (n = 18), the overall-survival time (OST) was significantly prolonged with low MDR1/P-gp expression level (P = 0.015). Expression levels of MRP2 and TOP1 did not correlate with OST. Moreover, the progression-free survival (PFS) in FIGO III patients showed a clear tendency to be associated with low MDR1/P-gp (P = 0.218) and TOP1 expression (P = 0.466), and negativity for MRP2 (P = 0.244).


CONCLUSIONS
MDR1/P-gp and MRP2 might have some additional predictive value for the clinical outcome of patients with advanced ovarian carcinoma.
Materna
Verena
V
Institute of Pathology, Charité Campus Mitte, D-10117 Berlin, Germany.
Pleger
Juliane
J
Hoffmann
Uwe
U
Lage
Hermann
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004264:DNA Topoisomerases, Type I; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C000715087:ABCC2 protein, human