MRP2 (ABCC2, cMOAT) expression in nuclear envelope of primary fallopian tube cancer cells is a new unfavorable prognostic factor

Abstract

ObjectiveTo determine the prognostic value of the immunohistochemical evaluation of the multidrug resistance-associated protein 2 (MRP2) expression, together with its subcellular localization in primary fallopian tube carcinomas (PFTCs).MethodsThe immunohistochemical analysis was performed using samples originating from 70 patients with PFTCs.Results(1) We documented that MRP2 can be localized in the plasma membrane (MRP2c), as well as in the nuclear envelope (MRP2n) of the PFTC cells. (2) Patients with more advanced stage, with progression of the disease and patients who died, showed significantly higher expression of the MRP2n. (3) Univariate and multivariate analyses showed that MRP2n is an unfavorable prognostic factor in PFTCs. (4) The analysis of the classic clinicopathological data revealed that only the FIGO stage had prognostic value, both in the univariate, as well as in multivariate analysis.Conclusions(1) This study suggests that MRP2n is a new disadvantageous prognostic factor in PFTCs and (2) that expression in nuclear envelope can be associated with lower differentiation of cancer cells and their resistance to the cisplatin. (3) We have also confirmed independent prognostic value of FIGO stage in PFTCs.

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

“…between MRP2 up-regulation and resistance towards platinum-based chemotherapy in ovarian cancer (Materna et al, 2005), small cell lung cancer (SCLC) (Halon et al, 2007). In a transport study with membrane vesicles, (Cui et al, 1999) it was found that MRP2-transfected HEK-293 cells showed higher V max and K m for anticancer agents.…”

Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies

“…Abnormal expression of MRP1 increases the efflux of Doxorubicin reducing its cytotoxic potential in ovarian cancer, leukemia and non-small cell lung cancer cells [160][161][162] . NRF2 dependant MRP2 upregulation has been reported to be a cause of resistance towards platinum based therapy in small cell lung cancer and ovarian cancer [163,164] ; Tamoxifen therapy towards breast cancer cells [165] . MRP3 was found to be more highly expressed in NSCLC than in SCLC, and NRF2 dependent MRP3 over expression causes intrinsic resistance of NSCLCs to anticancer drugs like vincristine, etoposide and Cisplatin [162] .…”

Primary Fallopian Tube Carcinoma

“…This was similar to most studies in the literature. 29,30 Although comprehensive staging of PFTC included pelvic and para-aortic lymphadenectomy in the National Comprehensive Cancer Network guidelines, 5 its role in the survival of PFTC remained controversial in the literature. For patients with positive lymph node involvement, the means of OS and DFS have been reported to be significantly shorter than those of the patients with negative lymph node involvement.…”