Topoisomerase IIα and other drug resistance markers in advanced non-small cell lung cancer

Resistance to chemotherapy is common in non-small cell lung cancer. The aim of this study was to investigate the prognostic impact of in vitro established drug resistance markers on the response to chemotherapy in patients with advanced non-small cell lung cancer. Samples of 38 patients were analyzed by immunohistochemical staining, for topoisomerase II alpha and II alpha, Ki-67, MRP and LRP. In addition, mutation analysis of the topoisomerase II alpha gene, the B/DNBS and the Tyr804 region, was performed. Lung tumor biopsies were taken prior for treatment with one of the following regimens; cisplatin/paclitaxel, cisplatin/VM26 or VP16, or carboplatin/VP16/ifosfamide. Seventeen patients obtained a partial response, 12 had stable disease and nine patients had progressive disease. None of the investigated markers was related with overall response rate. In one sample a point mutation in the B/DNBS region of the topo II alpha gene was detected which substitutes IIe(510) with Val. This tumor had a partial response to four courses of cisplatin/VP16 treatment. The survival analysis showed that the patients with high topo II alpha expressing tumors had a significantly worse survival compared with the patients with low or intermediate topo II alpha expressing tumors. In conclusion, no relation was observed between expression of topoisomerase II alpha, II beta, Ki-67, MRP or LRP and response rate. Furthermore, worse survival was seen in patients with high topoisomerase II alpha expressing tumors. In one tumor sample, a newly described mutation in the B/DNBS region of the topo II alpha gene was detected, which does not appear to be related to drug resistance. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.