Abstract
Non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) differ significantly in their clinical response to topoisomerase IIalpha (topo-IIalpha)-directed drugs, such as etoposide and teniposide, as NSCLC is virtually insensitive to single-agent therapy, while SCLC responds in two-thirds of cases. Preclinical studies have indicated that resistance to topo-IIalpha drugs depends on topo-IIalpha content and/or activity, the altered-topo-II multidrug resistance phenotype (at-MDR) and/or one of two different drug efflux pumps, P-glycoprotein (P-gp) and the multidrug resistance protein (MRP). Immunohistochemical analysis on paraffin-embedded tissue from 27 cases of untreated NSCLC and 29 cases of untreated SCLC (of which additional tumour biopsies after treatment with topo-IIalpha-directed drugs were available in ten cases) yielded the following results: NSCLC had significantly less topo-IIalpha than SCLC (P < 0.0001), as only 5 out of 27 NSCLC cases had > 5% positive cells compared with 28 out of 29 SCLC, and 0 out of 27 NSCLC had > 25% positive cells compared with 26 out of 29 SCLC. P-gp was detected in > 5% of cells in only 3 out of 27 NSCLC and in 6 out of 29 SCLC, and MRP in 5 out of 27 of NSCLC and 9 out of 29 SCLC. After treatment of patients with SCLC with either etoposide or teniposide, which are topo-IIalpha-directed drugs, there was an increase in MRP (P < 0.1) and P-gp (P < 0.05) positivity, while topo-IIalpha decreased (P < 0.05). In conclusion, the major difference between untreated NSCLC and SCLC was in topo-IIalpha content. In the small series of ten patients treated for SCLC, all three MDR phenotypes appeared to increase.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kreisholt, J., Sorensen, M., Jensen, P. et al. Immunohistochemical detection of DNA topoisomerase IIα, P-glycoprotein and multidrug resistance protein (MRP) in small-cell and non-small-cell lung cancer. Br J Cancer 77, 1469–1473 (1998). https://doi.org/10.1038/bjc.1998.241
Issue Date:
DOI: https://doi.org/10.1038/bjc.1998.241
This article is cited by
-
Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)
Pflügers Archiv - European Journal of Physiology (2007)
-
Relationship between methylation status of multi-drug resistance protein(MRP) and multi-drug resistance in lung cancer cell lines
Chinese Journal of Cancer Research (2007)
-
Comparison of Chemotherapy Response with P-Glycoprotein, Multidrug Resistance-Related Protein-1, and Lung Resistance-Related Protein Expression in Untreated Small Cell Lung Cancer
Lung (2005)
-
Genetic and Molecular Coordinates of Neuroendocrine Lung Tumors, with Emphasis on Small-cell Lung Carcinomas
Molecular Medicine (2002)
-
Simultaneous Quantitation of Topoisomerase II α and β Isoform mRNAs in Lung Tumor Cells and Normal and Malignant Lung Tissue
Laboratory Investigation (2000)