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 IIalpha 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.
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Authors | Areeg Faggad, Silvia Darb-Esfahani, Ralph Wirtz, Bruno Sinn, Jalid Sehouli, Dominique Könsgen, Hermann Lage, Aurelia Noske, Wilko Weichert, Ann-Christin Buckendahl, Jan Budczies, Berit M Müller, Nasr E Elwali, Manfred Dietel, Carsten Denkert |
Journal | Histopathology
(Histopathology)
Vol. 54
Issue 6
Pg. 657-66
(May 2009)
ISSN: 1365-2559 [Electronic] England |
PMID | 19438741
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- Multidrug Resistance-Associated Proteins
- RNA, Messenger
- multidrug resistance-associated protein 1
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
(genetics, metabolism)
- Carcinoma
(diagnosis, genetics, pathology)
- Drug Resistance, Neoplasm
- Female
- Humans
- Immunohistochemistry
- Middle Aged
- Multidrug Resistance-Associated Proteins
(genetics, metabolism)
- Ovarian Neoplasms
(diagnosis, genetics, pathology)
- Prognosis
- RNA, Messenger
(metabolism)
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