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

Anne Marie C. Dingemans, Jannette Van Ark-Otte, Simone Span, Giorgio V. Scagliotti, Paul Van Der Valk, Pieter E. Postmus, Giuseppe Giaccone*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

52 Citations (Scopus)

Abstract

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 IIα and IIβ, Ki-67, MRP and LRP. In addition, mutation analysis of the topoisomerase IIα 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 IIα gene was detected which substitutes IIe510 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 IIα expressing tumors had a significantly worse survival compared with the patients with low or intermediate topo IIα expressing tumors. In conclusion, no relation was observed between expression of topoisomerase IIα, IIβ, Ki-67, MRP or LRP and response rate. Furthermore, worse survival was seen in patients with high topoisomerase IIα expressing tumors. In one tumor sample, a newly described mutation in the B/DNBS region of the topo IIα gene was detected, which does not appear to be related to drug resistance.

Original languageEnglish
Pages (from-to)117-128
Number of pages12
JournalLung Cancer
Volume32
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by grant VU94-776 of the Dutch Cancer Society. The authors thank Karin Arkenbout, Isis Eizakkers and Adhiambo Witlox for technical assistance. RJ Scheper, A. Kikuchi and CJB Astaldi-Ricotti are acknowledged for providing antibodies.

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