Detection of drug resistance and P-glycoprotein in human renal cell carcinomas.
Expression of the multidrug-resistance gene product P-glycoprotein (P-170) was screened in 21 untreated human renal cell carcinomas using monoclonal antibodies (265/F4, C219) and immunoperoxidase staining. The inherent drug resistance of the same samples against doxorubicin was established by a short-term chemoresistance test in order to investigate the association between the expression of P-170 and intrinsic drug resistance in kidney cancers. P-glycoprotein could be demonstrated in 10 cases. Using the short-term test for predicting resistance, 17 resistant and 4 sensitive cancers were found. In vitro 10 of 17 resistant tumors revealed an increase of P-glycoprotein. On the other hand, in the sensitive tumor in vitro, an expression of P-glycoprotein could not be demonstrated. This investigation reveals that intrinsic drug resistance exists in many renal cell carcinomas and it is associated at least in part with increased expression of P-glycoprotein. The immunohistochemical results suggest that the presence of the P-glycoprotein may be useful as a marker for screening the multidrug-resistant phenotype in renal cell carcinomas and as an indicator of the therapeutic efficacy of multidrug-resistant kidney cancers.
Bak
M
M
German Cancer Research Center, Institute of Experimental Pathology, Heidelberg, FRG.
Efferth
T
T
Mickisch
G
G
Mattern
J
J
Volm
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000032:analysis* / Q000188:drug therapy; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000032:analysis* / Q000188:drug therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D004317:Doxorubicin