title: Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material.
abstract: Breast cancer resistance protein (BCRP/MXR/ABCP/ABCG2; hereafter ABCG2) is a member of the ATP-binding-cassette family of transporters that causes multi-drug resistance to various anticancer drugs. The expression of ABCG2 in human tumours and its potential involvement in clinical drug resistance are unknown. Recently, two monoclonal antibodies against human ABCG2 were produced, BXP-34 and BXP-21. This study describes an immunohistochemical method using BXP-21 to study ABCG2 expression in formalin-fixed, paraffin-embedded tissues. No staining was seen using BXP-34 with the same protocols. The expression of ABCG2 was then investigated in a panel of 150 untreated human solid tumours comprising 21 tumour types. Overall, ABCG2 expression was frequent. Specificity of immunohistochemistry was confirmed by the detection of a 72 kD band in western blotting. ABCG2 expression was seen in all tumour types, but it seemed more frequent in adenocarcinomas of the digestive tract, endometrium, and lung, and melanoma. Positive tumours showed membranous and cytoplasmic staining. In certain adenocarcinomas, prominent membranous staining was seen. Endothelial cells frequently displayed moderate to strong staining. ABCG2 is widely present in untreated human solid tumours and may represent a clinically relevant mechanism of drug resistance. Future studies in specific tumour types are needed to ascertain its clinical relevance. BXP-21 and the immunohistochemical protocol described here will be of value in these investigations.
authors.affiliation: Department of Medical Oncology, Laboratory of Translational Research, Catalan Institute of Oncology, Av. Gran Via Km 2,7, 08907 Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Julio E
authors.initials: JE
authors.lastname: Diestra
authors.forename: George L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: Isabel
authors.initials: I
authors.lastname: Català
authors.forename: Marc
authors.initials: M
authors.lastname: Maliepaard
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Jose R
authors.initials: JR
authors.lastname: Germà-Lluch
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Izquierdo
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D018432:Drug Resistance, Multiple; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D016612:Paraffin Embedding; D012680:Sensitivity and Specificity; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D005557:Formaldehyde