Multidrug resistance markers P-glycoprotein, multidrug resistance protein 1, and lung resistance protein in non-small cell lung cancer: prognostic implications.
OBJECTIVE
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.
Berger
Walter
W
Division of Applied Oncology, Institute of Cancer Research, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria. walter.berger@meduniwien.ac.at
Setinek
Ulrike
U
Hollaus
Peter
P
Zidek
Thomas
T
Steiner
Elisabeth
E
Elbling
L
L
Cantonati
H
H
Attems
Johannes
J
Gsur
Andrea
A
Micksche
Michael
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D018432:Drug Resistance, Multiple; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein