Topoisomerase II alpha 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 establi shed drug resistance markers on the response to chemotherapy in patients wi th advanced non-small cell lung cancer. Samples of 38 patients were analyze d 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 bi opsies were taken prior for treatment with one of the following regimens; c isplatin/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 wa s 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 cispla tin/VP16 treatment. The survival analysis showed that the patients with hig h topo II alpha expressing tumors had a significantly worse survival compar ed with the patients with low or intermediate topo II alpha expressing tumo rs. In conclusion, no relation was observed between expression of topoisome rase II alpha, II beta, Ki-67, MRP or LRP and response rate. Furthermore, w orse survival was seen in patients with high topoisomerase II alpha express ing tumors. In one tumor sample, a newly described mutation in the B/DNBS r egion of the topo II alpha gene was detected, which does not appear to be r elated to drug resistance. (C) 2001 Elsevier Science Ireland Ltd. All right s reserved.