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Clinical Significance of the Resistance Proteins LRP, Pgp, MRP1, MRP3, and MRP5 in Epithelial Ovarian Cancer
  1. Iva Sedláková, MD, PhD*,
  2. Jan Laco, MD, PhD,
  3. Katerina Caltová, BSc, PhD,
  4. Miroslav Cervinka, MD, PhD,
  5. Jindrich Tošner, MD, PhD*,
  6. Adam Rezác, MD* and
  7. Jirí Špacek, MD, PhD*
  1. *Department of Gynecology and Obstetrics, University Hospital Hradec Králové and Medical Faculty;
  2. Fingerland Department of Pathology, University Hospital Hradec Králové; and
  3. Department of Medical Biology and Genetics, Medical Faculty Hradec Králové, Hradec Králové, Czech Republic.
  1. Address correspondence and reprint requests to Iva Sedláková, MD, PhD, Department of Gynecology and Obstetrics, University Hospital, Sokolská 581, 500 05 Hradec Králové, Czech Republic. E-mail: sedlakiva{at}seznam.cz.

Abstract

Objective This study aimed to evaluate the correlation between the expressions of lung resistance protein (LRP), P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP)-1, MRP3, and MRP5 and histopathological parameters and clinical outcome, and to determine the predictive and prognostic value of these transport proteins in patients with ovarian cancer.

Methods Tumor samples from 111 chemonaive patients with epithelial ovarian cancer who underwent primary surgery from 2006 to 2010 were immunohistochemically stained for LRP, Pgp, MRP1, MRP3, and MRP5 expressions.

Results MRP1 expression was greater among patients with late disease than among patients with early stage ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) I + II, 71.6% (confidence interval, 60–100); FIGO III + IV, 83.6% (confidence interval, 100–100); P = 0.03]. The histological subtype correlated with the expressions of LRP, Pgp, MRP1, and MRP3. Relapse of disease during the next 24 months occurred more often among patients with higher Pgp and MRP1 than among patients with lower Pgp and MRP1 expressions. FIGO stage, histological type, debulking efficiency, strong Pgp expression, and strong MRP1 expression correlated significantly with shorter progression-free survival (log-rank test, P = 0.001, P = 0.004, P = 0.001, P = 0.051, and P = 0.046, respectively). FIGO stage, histological type, debulking efficiency, and strong MRP1 expression correlated with poor patient survival (log-rank test, P = 0.001, P = 0.042, P = 0.005, and P = 0.018, respectively).

Conclusions Pgp and MRP1 expressions were clinically significant in patients with ovarian cancer. Pgp and MRP1 may be reliable, independent predictive and prognostic factors regarding the clinical outcome of ovarian cancer. MRP3 is less important as a predictive and prognostic factor than MRP1 expression. MRP5 and LRP expressions were not applicable prognostic parameters regarding ovarian cancer.

  • Ovarian carcinoma
  • Drug resistance
  • Predictive factor
  • Prognostic factor
  • MRP

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Footnotes

  • Supported by the Ministry of Health, Czech Republic (NT 14107 IGA MH CR).

  • The authors declare no conflicts of interest.

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