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- Title
Expression of multidrug resistance-associated protein 1 in invasive ovarian carcinoma: implication for prognosis.
- Authors
Faggad, Areeg; Darb-Esfahani, Silvia; Wirtz, Ralph; Sinn, Bruno; Sehouli, Jalid; Könsgen, Dominique; Lage, Hermann; Noske, Aurelia; Weichert, Wilko; Buckendahl, Ann-Christin; Budczies, Jan; Müller, Berit M; Elwali, Nasr E; Dietel, Manfred; Denkert, Carsten
- Abstract
Aims: 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. Methods and 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 IIα expression both at mRNA and protein level ( P < 0.001 and P = 0.023, respectively). Conclusion: 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.
- Subjects
DRUG resistance; OVARIAN cancer; MULTIVARIATE analysis; TUMOR suppressor proteins; DRUG therapy; GENETIC regulation
- Publication
Histopathology, 2009, Vol 54, Issue 6, p657
- ISSN
0309-0167
- Publication type
Article
- DOI
10.1111/j.1365-2559.2009.03297.x