Intracellular localization of multidrug resistance associated protein (MRP) and atypical multidrug resistance phenomenon in non-small cell lung cancer

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Multidrug resistance-associated protein (MRP) is one of the major factors for non-P-glycoprotein (PGp)-mediated multidrug-resistance. It is unclear how MRP expression is regulated in NSCLC.In this study, we examined MRP and mutant p53 expression in 107 NSCLC by immunohistochemical procedures. Forty-seven of these 107 NSCLC cases were positive for MRP in the cytoplasm. Mutant p53-positive NSCLC showed a significant correlation with MRP overexpression. Coexpression of MRP and p53 in the same cells of NSCLC was confirmed by double staining procedures. Twenty-six patients with MRP-positive tumors who underwent postoperative chemotherapy with MRP-related anticancer drugs showed significantly poorer prognosis than those with MRP-negative tumors. This correlation between MRP expression and prognosis was also seen in stage Ill patients, and in patients with squamous cell carcinoma. NSCLC patients with coexpression of MRP and p53 showed poorer prognosis than those without MRP and p53. These results suggest that MRP overexpression affected by mutant p53 has a significant effect on prognosis through atypical non-PGp-mediated multidrug resistance in NSCLC.