title: Differentiation dependent expression of P-glycoprotein in the normal and neoplastic human kidney.
abstract: Adult renal cell carcinoma (RCC) is clinically resistant to chemotherapy. However, in nephroblastoma (NBL) chemotherapy has increased survival dramatically. We studied the P-glycoprotein (P-gp) expression of 18 RCC and 9 NBL as well as 1 benign renal adenoma and fetal renal tissue using three different monoclonal antibodies (MRK-16, C-219, JSB-1). P-gp was found positive with all three antibodies in 12/18 RCC, while only 2 tumors were completely negative. Staining varied with respect to intensity and number of positive cells [5%-90%]. Intense staining was seen at the apical side of malignant tubules in well differentiated parts of RCC and in tubular structures of the benign renal adenoma. Poorly differentiated parts of the tumors showed less staining. In NBL blastemal parts were negative. In 4/8 specimens showing focal epithelial differentiation, however, the luminal side of more differentiated tubular structures did stain, strongly resembling P-gp staining in the developing fetal human kidney. These results indicate that P-gp expression in normal (fetal) human kidney as well as in benign and malignant tumors derived from this organ depends on the degree of differentiation of tubules, which may have implications for chemotherapy sensitivity in both malignant tumors.
authors.affiliation: Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: C K
authors.initials: CK
authors.lastname: van Kalken
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: M M
authors.initials: MM
authors.lastname: Hadisaputro
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: H J
authors.initials: HJ
authors.lastname: Broxterman
authors.forename: C M
authors.initials: CM
authors.lastname: Kuiper
authors.forename: G L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: A J
authors.initials: AJ
authors.lastname: Veerman
authors.forename: C J
authors.initials: CJ
authors.lastname: Meyer
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012016:Reference Values; D009396:Wilms Tumor / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins