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Multidrug resistance markers P-glycoprotein, multidrug resistance protein 1, and lung resistance protein in non-small cell lung cancer: prognostic implications

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Abstract

Purpose

The aim of this retrospective study was to comparatively investigate the expression of the three drug-resistance genes P-glycoprotein (P-gp), multidrug-resistance protein 1 (MRP1), and lung resistance protein (LRP), in non-small cell lung cancer (NSCLC) tissues, and to assess possible associations with clinicopathologic features.

Methods

Tumor specimens from 126 patients were analyzed by immunohistochemistry and, in selected cases, by reverse transcriptase polymerase chain reaction (RT-PCR), and data were statistically analyzed by SPSS.

Results

The mean expression levels of tumor tissues in the case of P-gp and LRP did not exceed the one of normal epithelia, while MRP1 was significantly enhanced in NSCLC. A weak association was observed between higher grading and P-glycoprotein expression ( p <0.08) as well as lower grading and MRP1 expression in the case of adenocarcinoma ( p <0.05). MRP1 levels were highest in TNM stage I and declined with advanced stage ( p <0.03). A significant association was found between high MRP1 levels and longer overall survival ( N =115, p <0.04), which was highly significant in the patient group never treated with chemotherapy ( N =77; p <0.007). P-gp expression was enhanced in those patients who had received chemotherapy before surgery ( p <0.05).

Conclusions

Our data point towards a major role of MRP1 in the intrinsic treatment resistance of NSCLC and suggest, in addition, a significant activation of P-gp expression during chemotherapy.

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Acknowledgements

The work has been supported by the Jubiläumsfonds der Österreichischen Nationalbank Bank, Grant 7258 and the Herzfelder’schen Familienstiftung

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Authors and Affiliations

  1. Divisions of Applied & Experimental Oncology, Institute of Cancer Research, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria

    Walter Berger, Elisabeth Steiner, L. Elbling, Andrea Gsur & Michael Micksche

  2. Institute for Pathology and Bacteriology, Otto Wagner Hospital Baumgartner Höhe, Vienna, Austria

    Ulrike Setinek, H. Cantonati & Johannes Attems

  3. Department of Thoracic Surgery, Otto Wagner Hospital Baumgartner Höhe, Vienna, Austria

    Peter Hollaus

  4. Division of Epidemiology, Institute of Cancer Research, Medical University Vienna, Vienna, Austria

    Thomas Zidek

Authors
  1. Walter Berger
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  2. Ulrike Setinek
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  3. Peter Hollaus
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  4. Thomas Zidek
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  5. Elisabeth Steiner
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  6. L. Elbling
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  7. H. Cantonati
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  8. Johannes Attems
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  9. Andrea Gsur
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  10. Michael Micksche
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Correspondence to Walter Berger.

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Berger, W., Setinek, U., Hollaus, P. et al. Multidrug resistance markers P-glycoprotein, multidrug resistance protein 1, and lung resistance protein in non-small cell lung cancer: prognostic implications. J Cancer Res Clin Oncol 131, 355–363 (2005). https://doi.org/10.1007/s00432-004-0653-9

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  • DOI: https://doi.org/10.1007/s00432-004-0653-9

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