MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN AND MUTANT P53 PROTEIN EXPRESSION IN NONSMALL CELL LUNG-CANCER

Multidrug resistance-associated protein (MRP) is one of the major fact ors for non-P-glycoprotein (PGp)-mediated multidrug resistance. We rep orted previously that overexpression of the MRP gene was related to th e prognosis of non-small cell lung cancer (NSCLC). It is unclear how M RP expression is regulated in NSCLC. In this study, we examined MRP an d mutant p53 expression in 107 NSCLCs by immunohistochemical procedure s, Forty-seven (43.9%) of these 107 NSCLCs were positive for MRP in th e cytoplasm. Mutant p53-positive NSCLC showed a significant correlatio n with MRP overexpression (P = .011). Coexpression of MRP and p53 in t he same cells of NSCLC was confirmed by double-staining procedures. Tw enty-six patients with MRP-positive tumors who underwent postoperative chemotherapy with MRP-related anticancer drugs (vindesine and etoposi de) had significantly poorer prognoses than did those with MRP-negativ e tumors (P = .017). This correlation between MRP expression and progn osis was also seen in Stage III patients (P = .022) and in patients wi th squamous cell carcinoma (P = .062). NSCLC patients with co-expressi on of MRP and p53 showed poorer prognoses than did those without MRP a nd p53 (P = .014). These results suggested that MRP overexpression aff ected by mutant p53 had a significant effect on prognosis through atyp ical non-PGp-mediated multidrug resistance in NSCLC.