Prognostic significance of Pgp, MRP1, and MRP3 in ovarian cancer patients


Authors: I. Sedláková 1;  J. Laco 2;  J. Tošner 1;  J. Špaček 1
Authors‘ workplace: Porodnická a gynekologická klinika LF UK a FN, Hradec Králové, přednosta doc. MUDr. J. Špaček, PhD., IFEPAG 1;  Fingerlandův ústav patologie LF UK a FN, Hradec Králové, přednosta prof. MUDr. A. Ryška, Ph. D. 2
Published in: Ceska Gynekol 2015; 80(6): 405-413

Overview

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

Design:
Prospective study.

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

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

Results:
The histological subtype of epithelial ovarian cancer correlated with the expression of PgP, MRP1, and MRP3. The lowest incidence of Pgp and MRP1 expression was documented in endometrioid ovarian cancers (P = 0.151, P = 0.013). Patients with advanced ovarian cancer (FIGO III+IV) had higher MRP1 expression than those with early stage ovarian cancer (Med MRP1 FIGO I+II 80%; CI: 60–100; FIGO III+IV 100%; CI: 90–100; P = 0.100). An association was observed between MRP1 and tumor grade (Med MRP1 G1 80% (CI: 0–100), G2 80% (CI: 30–100), G3 100% (CI: 90–100); P < 0.001). There was no relationship between the size of the residual tumor after primary surgery and any resistance proteins. Patients with complete response after primary treatment had lower levels of LRP, Pgp, and MRP1 expression than other patients. Patients with higher Pgp and MRP1 expression had relapse of disease during the following 24 months more often than patients with lower Pgp and MRP1 expression. FIGO stage, histological type, debulking efficiency, and Pgp and MRP1 expression correlated with poor patient survival (P < 0.001, P < 0.001, P < 0.001, P = 0.040, P = 0.026).

Conclusion:
We found prognostic significance of Pgp, MRP1 and MRP3 expression in ovarian cancer patients. MRP1 have some additional prognostic value for the clinical outcome of patients with ovarian carcinoma.

Keywords:
ovarian carcinoma, Pgp/ABCB1, MRP1/ABCC1, MRP3/ABCC3, drug resistance


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Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine
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