Expression of multidrug resistance-associated protein 1 in invasive ovarian carcinoma: implication for prognosis.
OBJECTIVE
Multidrug resistance is a major impediment in chemotherapeutic treatment of ovarian carcinoma patients. The aim of this study was to investigate the expression of multidrug resistance-associated protein 1 (MRP1) and to assess the possible associations with clinicopathological variables and patient outcome in primary ovarian carcinoma.


RESULTS
Tumour specimens from 129 patients were obtained before chemotherapy and analysed by immunohistochemistry on tissue microarrays, and by real-time reverse transcriptase-polymerase chain reaction on RNA extracted from formalin-fixed paraffin-embedded tissue specimens using a new technique. Significantly increased MRP1 protein expression was observed in high-grade tumours (P = 0.005) and advanced International Federation of Gynaecology and Obstetrics stages (P = 0.036). On univariate Kaplan-Meier analysis, patients with higher expression of MRP1 protein had significantly decreased overall survival (P = 0.006). On multivariate Cox regression analysis, MRP1 protein expression retained its significance as an independent negative prognostic marker for overall survival (hazard ratio = 6.52, P = 0.003). Furthermore, MRP1 expression correlated with topoisomerase IIalpha expression both at mRNA and protein level (P < 0.001 and P = 0.023, respectively).


CONCLUSIONS
In summary, in patients with primary ovarian cancer, overexpression of MRP1 is an adverse marker for patient outcome and cancer aggressiveness. Our data provide a translational basis for further clinical studies on the predictive value of MRP1 expression for response to chemotherapy.
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Areeg
A
Faggad
Silvia
S
Darb-Esfahani
Ralph
R
Wirtz
Bruno
B
Sinn
Jalid
J
Sehouli
Dominique
D
Könsgen
Hermann
H
Lage
Aurelia
A
Noske
Wilko
W
Weichert
Ann-Christin
AC
Buckendahl
Jan
J
Budczies
Berit M
BM
Müller
Nasr E
NE
Elwali
Manfred
M
Dietel
Carsten
C
Denkert
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism
D014408:Biomarkers, Tumor; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C421109:multidrug resistance-associated protein 1