Expression of multidrug resistance proteins P-glycoprotein, multidrug resistance protein 1, breast cancer resistance protein and lung resistance related protein in locally advanced bladder cancer treated with neoadjuvant chemotherapy:: Biological and clinical implications

Purpose: Resistance to chemotherapy is a major obstacle to overcome in the conservative treatment of patients with locally advanced bladder cancer (LABC). We investigated the predictive value of the response to neoadjuvant chemotherapy (NACT) and prognosis of the expression of multidrug resistance (MDR) related proteins, P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP) and lung resistance related protein/major vault protein (LRP/MVP) in LABC. Materials and Methods: Using immunohistochemistry we studied the expression of MDR proteins in tumors from 83 patients with LABC treated with NACT using a bladder sparing approach. Expression was related to the response to NACT, bladder preservation and prognosis. Results: P-gp, MRP1, BCRP and LRP/MVP were expressed at high levels in 53%, 59%, 28% and 70% of cases, respectively. P-gp expression correlated with shorter progression-free survival (p=0.04) but not with overall survival. Surprisingly MRP1 expression correlated with a higher response (p=0.005) and a higher probability of bladder preservation following NACT (p=0.001). BCRP did not show any prognostic impact. High LRP/MVP expression was significantly associated with a worse response to NACT and a decreased probability of bladder preservation (p=0.035). Conclusions: Our data suggest that MRP1 and LRP/MVP may be useful in combination with other clinicopathological prognostic factors for selecting patients with LABC to be candidates for bladder preservation after NACT. A large prospective study is warranted to confirm the prognostic value of these MDR proteins.