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. 2005 Jun;131(6):355-63. doi: 10.1007/s00432-004-0653-9. Epub 2005 Jan 27.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adenocarcinoma, Bronchiolo-Alveolar / metabolism
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology
  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers, Tumor / metabolism*
  • Bronchi / metabolism
  • Bronchi / pathology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Resistance, Multiple*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Cells, Cultured
  • Vault Ribonucleoprotein Particles / metabolism*


  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Vault Ribonucleoprotein Particles
  • major vault protein