Immunohistochemical Detection of Multidrug Resistance Protein in Human Lung Cancer and Normal Lung1

Monoclonal antibody QCRL-i is highly specific for a defined linear epitope in a relatively poorly conserved region of the human multidrug resistance protein (MRP). We have used QCRL-i to examine MRP expression in archival and fresh snap-frozen samples of untreated small cell (SC) and non-small cell (NSC) lung cancers (LCs), as well as normal lung. We found that the majority (87%) of all histological subtypes of NSCLC had detectable levels of MRP in most of the tumor mass. In a substantial proportion of adenocarcinomas (55%) and squamous cell carcinomas (28%), immunoreactivity approached that obtained with the highly midtidrug resistant cell line H69AR from which the MRP was originally cloned. Both the level and frequency of MRP expression in untreated SCLC was significantly lower than in NSCLC. The MRP was detectable in only 56% of SCLC tumors and, in most cases, was expressed in small focal clusters of cells. Immunofluorescence studies of tumor tissue and normal lung confirmed the plasma membrane location of the MRP. However, in normal bronchial epitheium and seromucous glands, unlike in tumor cells, the MRP was detected only on basolateral membranes. In addition, strong MRP immunoreactivity was detected in reactive type II pneumocytes present in hyperplastic alveoli, but not in normal type I and type II pneumocytes. No potentially conReceived 3/17/98; accepted 6/10/98. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported by grant MT-i0519 from the Medical Research Council of Canada. R. G. D is the Stauffer Research Professor of Queen’s University. S. P. C. C. is a Senior Scientist and B. G. C. is a Clinician Scientist ofCancer Care Ontario. S. R. W. was supported by an Ontario Graduate Scholarship, and D. R. H. was supported by a Medical Research Council of Canada Studentship. 2 Current address: Department of Anatomy and Cell Biology, Queen’s University, Kingston, Ontario, Canada K7L 3N6. 3 To whom requests for reprints should be addressed, at Cancer Research Laboratories, Room 328, Botterell Hail, Queen’s University, Kingston, Ontario, Canada, K7L 3N6. Phone: 6i3-545-298i; Fax: 6i3545-6830; E-mail: [email protected]. founding correlation independent of its possible role in drug resistance was observed between MRP expression in untreated NSCLC and any clinicopathological parameter examined, including overall survival.