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Expression of multidrug resistance-associated protein 1 in invasive ovarian carcinoma: implication for prognosis.

AbstractAIMS:
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.
AuthorsAreeg 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
JournalHistopathology (Histopathology) Vol. 54 Issue 6 Pg. 657-66 (May 2009) ISSN: 1365-2559 [Electronic] England
PMID19438741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • multidrug resistance-associated protein 1
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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