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

多药耐药相关蛋白（MRP）是非P-糖蛋白（PGp）介导的多药耐药的主要因素之一。本研究采用免疫组化方法检测了107例NSCLC中MRP和突变型p53的表达。这107例NSCLC中有47例胞浆MRP阳性。突变型p53阳性NSCLC与MRP过表达显著相关。MRP和p53在NSCLC同一细胞中的共表达通过双重染色程序证实。26例MRP阳性肿瘤患者术后接受MRP相关抗癌药物化疗，其预后明显差于MRP阴性肿瘤患者。MRP表达与预后之间的相关性也见于III期患者和鳞状细胞癌患者。MRP和p53共表达的NSCLC患者的预后比MRP和p53阴性者差。这些结果表明，MRP过度表达的突变型p53的影响，通过非典型的非PGp介导的多药耐药的NSCLC的预后有显着的影响。

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.