Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues.
BACKGROUND
The recently discovered LRP protein has been shown to be involved in drug resistance and possibly in detoxification processes.


METHODS
To study the relation between LRP expression and exposure to cigarette smoke, LRP immunoreactivity was evaluated in 39 paraffin embedded normal lung tissues derived from patients operated on for pneumothorax, and related to amount of pack years smoked. We also studied the LRP protein expression in 36 non-small-cell lung cancer (NSCLC) samples and related the expression to patient characteristics and survival. Furthermore 17 lung tumor samples (10 NSCLC and 7 SCLC) derived from patients treated with chemotherapy were analysed in order to investigate the relation between LRP or MRP expression and the patient's response to chemotherapy.


RESULTS
In the normal lung tissues, LRP intensity levels were not correlated to the amount of pack years smoked, although a trend was seen for higher LRP intensity levels in patients who smoked more than 10 pack years. LRP expression was significantly higher in NSCLC samples than in SCLC samples, and all SCLC samples displayed very low LRP expression. Within NSCLC, squamous cell and adenocarcinomas had higher LRP expression than large cell undifferentiated and mixed tumors. In NSCLC patients LRP expression was not a prognostic factor for survival. At initial analysis LRP expression levels did not predict for the response to chemotherapy. Only 3 out of 17 patients expressed MRP, and all SCLC samples were MRP negative.


CONCLUSIONS
Striking different expression levels were seen between NSCLC and SCLC for both LRP and MRP. In a preliminary analysis LRP expression was not predictive for response to chemotherapy in lung cancer patients. In pneumothorax patients LRP levels were not correlated with the amount of pack years smoked.
Dingemans
A M
AM
Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
van Ark-Otte
J
J
van der Valk
P
P
Apolinario
R M
RM
Scheper
R J
RJ
Postmus
P E
PE
Giaccone
G
G
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008658:Inactivation, Metabolic; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D012907:Smoking / Q000378:metabolism; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein