Immunohistochemical Expression of MRP2 and Clinical Resistance to Platinum-based Chemotherapy in Small Cell Lung Cancer

Abstract

Determining an effective predictor of clinical drug resistance in small cell lung cancer (SCLC) is considered to be important. In this study, the relationship between the expression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and MRP2, which are the members of ATP-binding cassette superfamily transporter, and of the p53 tumor suppressor gene and the response to chemotherapy were analysed. The expression of P-gp, MRP1, MRP2, and p53 was determined by an immunohistochemical analysis of transbronchial biopsy (TBB) specimens from 61 SCLC patients. The relationship of such expression was also investigated regarding chemotherapy and clinicopathological factors. The response rate in the MRP2-negative group was significantly higher than that in the MRP2-positive group (88% versus 50%). The P-gp-negative group responded significantly better to chemotherapy than the P-gp-positive group, with a response rate of 81% versus 39%. No relationship could be found between the response to chemotherapy and immunostaining for MRP1 or p53. In 37 patients treated with platinum-based chemotherapy, the response rate of patients in the MRP2-negative group was significantly higher than that in the positive group (92% versus 50%). In a multiple logistic regression analysis, MRP2 as well as P-gp were shown to be statistically significant predictors of chemotherapy resistance. These results suggest that immunostaining of MRP2 for TBB specimens may help to predict clinical resistance to platinum agents. This is the first report which indicates that the immunohistochemical expression of MRP2 is positively related to a clinical resistance to platinum.