BACKGROUND: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if the coexpression of ABC transporters and survivin was associated with R-CHOP treatment response. METHODS: The expression of Bcl-2, survivin, P-glycoprotein/ABCB1, MRP1/ABCC1, and BCRP/ABCC2 was analyzed using immunohistochemistry in tumor specimens obtained from patients with DLBCL, and classified according to the treatment response as Remission, Relapsed, and (primary) Refractory groups. All patients received R-CHOP or equivalent treatment. RESULTS: Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in the Refractory and Relapsed groups (p < 0.05 vs. Remission), respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response. CONCLUSIONS: DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.

Center for Biomedical Research Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Clinic of Hematology University Clinical Center of Serbia 2 Pasterova 11000 Belgrade Serbia

Department for Experimental Toxicology and Pharmacology National Poison Control Centre Military Medical Academy Crnotravska 17 11000 Belgrade Serbia

Department of Analytical Chemistry Faculty of Chemistry University of Belgrade Studenski trg 16 11000 Belgrade Serbia

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralove Czech Republic

Department of Gynecology and Obstetrics Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Department of Hematology Clinic of Internal Medicine University Clinical Center Republic of Srpska 12 Beba 78000 Banja Luka Bosnia and Herzegovina

Department of Hematology Faculty of Medicine University of Belgrade 11000 Belgrade Serbia

Department of Internal Medicine Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Department of Pathology Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Department of Pharmacology Toxicology and Clinical Pharmacology Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Department of Surgery Faculty of Medicine University of Banja Luka Save Mrkalja 14 78000 Banja Luka Bosnia and Herzegovina

Institute for Medical Research National Institute of the Republic of Serbia Department for Cardiovascular Research University of Belgrade Dr Subotića 4 11000 Belgrade Serbia

Medical Faculty of the Military Medical Academy University of Defence Crnotravska 17 11000 Belgrade Serbia

Special Police Unit Ministry of Interior Trebevićka 12 A 11030 Belgrade Serbia

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