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Expression of multidrug resistance‐associated protein 1 in invasive ovarian carcinoma: implication for prognosis
Author(s) -
Faggad Areeg,
DarbEsfahani Silvia,
Wirtz Ralph,
Sinn Bruno,
Sehouli Jalid,
Könsgen Dominique,
Lage Hermann,
Noske Aurelia,
Weichert Wilko,
Buckendahl AnnChristin,
Budczies Jan,
Müller Berit M,
Elwali Nasr E,
Dietel Manfred,
Denkert Carsten
Publication year - 2009
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2009.03297.x
Subject(s) - ovarian carcinoma , immunohistochemistry , tissue microarray , multiple drug resistance , medicine , ovarian cancer , oncology , topoisomerase , chemotherapy , biology , univariate analysis , proportional hazards model , hazard ratio , cancer , drug resistance , carcinoma , multivariate analysis , confidence interval , enzyme , biochemistry , microbiology and biotechnology
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.