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Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues
Authors:Dingemans, A.-M. C.   van Ark-Otte, J.   van der Valk, P.   Apolinario, R. M.   Scheper, R. J.   Postmus, P. E.   Giaccone, G.
Affiliation:1Department of Medical Oncology, University Hospital Vrije Universiteit Amsterdam, The Netherlands
2Department of Pulmonary Medicine University Hospital Vrije Universiteit Amsterdam, The Netherlands
Department of Pathology, University Hospital Vrije Universiteit Amsterdam, The Netherlands
Abstract:BACKGROUND:: The recently discovered LRP protein has been shown to be involvedin drug resistance and possibly in detoxification processes. MATERIALS AND METHODS:: To study the relation between LRP expression and exposure tocigarette smoke, LRP immunoreactivity was evaluated in 39 paraffinembedded normal lung tissues derived from patients operatedon for pneumothorax, and related to amount of pack years smoked.We also studied the LRP protein expression in 36 non-small-celllung cancer (NSCLC) samples and related the expression patientcharacteristics and survival. Furthermore 17 lung tumor samples(10 NSCLC and 7 SCLC) derived from patients treated with chemotherapywere analysed in order to investigate the relation between LRPor MRP expression and patient's response to chemotherapy. RESULTS:: In the normal lung tissues, LRP intensity levels were not correlatedto the amount of pack years smoked, although a trend was seenfor higher LRP intensity levels in patients who smoked morethan 10 pack years. LRP expression was significantly higherin NSCLC samples than in SCLC samples, and all SCLC samplesdisplayed very low LRP expression. Within NSCLC, squamous celland adenocarcinomas had higher LRP expression than large cellundifferentiated and mixed tumors. In NSCLC patients LRP expressionwas not a prognostic factor for survival. At initial analysisLRP expression levels did not predict for the response to chemotherapy.Only 3 out of 17 patients expressed MRP, and all SCLC sampleswere MRP negative. CONCLUSION:: Striking different expression levels were seen between NSCLCand SCLC for both LRP and MRP. In a preliminary analysis LRPexpression was not predictive for response to chemotherapy inlung cancer patients. In pneumothorax patients LRP levels werenot correlated with the amount of pack years smoked. detoxification, immunohistochemistry, LRP, lung cancer, MRP, multidrug resistance
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