Drug resistance proteins LRP, Pgp, MRP1, MRP3 and MRP5 in ovarian cancer patients


Authors: I. Sedláková 1;  J. Laco 2;  J. Tošner 1;  J. Špaček 1;  E. Čermáková 3
Authors‘ workplace: Porodnická a gynekologická klinika LF UK a FN, Hradec Králové, přednosta doc. MUDr. J. Špaček, Ph. D., IFEPAG 1;  Fingerlandův ústav patologie LF UK a FN, Hradec Králové, přednosta prof. MUDr. A. Ryška, Ph. D. 2;  Ústav lékařské biofyziky LF UK, Hradec Králové, přednosta doc. MUDr. J. Hanuš, CSc. 3
Published in: Čes. Gynek.2013, 78, č. 6 s. 545-553
Category: Original Article

Overview

Objective:
To evaluate the correlation of drug resistance proteins LRP (Lung Resistance Protein), Pgp (P-glycoprotein), MRP1 (Multidrug Related Protein, Multidrug Resistance–Associated Protein), MRP3 a MRP5 with clinical – pathological factors and to find the clinical outcome of these data in ovarian cancer patients.

Design:
Prospective study.

Setting:
Department of Obstetrics and Gynecology, Charles University in Prague, Faculty of Medicine and University Hospital Hradec Kralove.

Methods:
111 patients with epithelial ovarian cancer who underwent primary surgery from 2006–2010 had specimens stained with imunohistochemistry for LRP, Pgp, MRP1, MRP3, MRP5.

Results:
The histological subtype of epithelial ovarian cancer correlated to the LRP, Pgp, MRP1 and MRP3 expression. Patients with late ovarian cancer had a higher MRP1 compared to early stage ovarian cancer (I+II 71.6% (CI 60–100), III+IV 83.6% (CI 100–100),p = 0.03). Correlation of MRP1 with grading was found(G1 60.83% (CI 10–100), G2 36.80% (CI 20–100),G3 88.87% (CI 100–100), p = 0.039). Patients with high Pgp, MRP1 and MRP3 expression had significantly shorter progression-free survival. (Kaplan-Meier test – PFS, Pgp < 85% Med PFS 23 months (CI 8–37) vs > 85% Med PFS 11 months (CI 7–17), p = 0.054), (MRP1 < 85% Med PFS 33 months (CI 11–49) vs > 85% Med PFS 11 months(CI 7–16), p = 0.046).

Conclusion:
We found clinical significance of LRP, Pgp, MRP1 and MRP3 expression in ovarian cancer patients. MRP5 expression did not correlate with neither histo-pathological parameters nor progression free survival. MRP1 have some additional predictive and prognostic value for the clinical outcome of patients with ovarian carcinoma.

Keywords:
ovarian carcinoma – LRP – Pgp/ABCB1 – MRP1/ABCC1 – MRP3/ABCC3 – MRP5/ABCC5 – drug resistance


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Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine

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