Bak M, Efferth T, Mickisch G, Mattern J, Volm M
German Cancer Research Center, Institute of Experimental Pathology, Heidelberg, FRG.
Eur Urol. 1990;17(1):72-5. doi: 10.1159/000464005.
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.
采用单克隆抗体(265/F4、C219)和免疫过氧化物酶染色法,对21例未经治疗的人类肾细胞癌进行多药耐药基因产物P-糖蛋白(P-170)表达的筛选。通过短期化疗耐药试验确定相同样本对阿霉素的固有耐药性,以研究P-170表达与肾癌固有耐药性之间的关联。10例病例可检测到P-糖蛋白。采用短期试验预测耐药性,发现17例耐药癌和4例敏感癌。在体外,17例耐药肿瘤中有10例显示P-糖蛋白增加。另一方面,在体外敏感肿瘤中未检测到P-糖蛋白的表达。这项研究表明,许多肾细胞癌存在固有耐药性,且至少部分与P-糖蛋白表达增加有关。免疫组化结果表明,P-糖蛋白的存在可能作为筛选肾细胞癌多药耐药表型的标志物以及多药耐药性肾癌治疗效果的指标。