Multidrug resistance markers P-glycoprotein, multidrug resistance protein 1, and lung resistance protein in non-small cell lung cancer: prognostic implications

Purpose: The aim of this retrospective study was to comparatively investigate the expression of the three drug-resistance genes P-glycoprotein (P-gp), multidrug-resistance protein 1 (MRP1), and lung resistance protein (LRP), in non-small cell lung cancer (NSCLC) tissues, and to assess possible associations with clinicopathologic features. Methods: Tumor specimens from 126 patients were analyzed by immunohistochemistry and, in selected cases, by reverse transcriptase polymerase chain reaction (RT-PCR), and data were statistically analyzed by SPSS. Results: The mean expression levels of tumor tissues in the case of P-gp and LRP did not exceed the one of normal epithelia, while MRP1 was significantly enhanced in NSCLC. A weak association was observed between higher grading and P-glycoprotein expression (p < 0.08) as well as lower grading and MRP1 expression in the case of adenocarcinoma (p < 0.05). MRP1 levels were highest in TNM stage I and declined with advanced stage (p < 0.03). A significant association was found between high MRP1 levels and longer overall survival (N =115, p < 0.04), which was highly significant in the patient group never treated with chemotherapy (N =77; p < 0.007). P-gp expression was enhanced in those patients who had received chemotherapy before surgery ( p < 0.05). Conclusions: Our data point towards a major role of MRP1 in the intrinsic treatment resistance of NSCLC and suggest, in addition, a significant activation of P-gp expression during chemotherapy.