Expression of resistance factors (P‐glycoprotein, glutathione S‐transferase‐π, and topoisomerase II) and their interrelationship to proto‐oncogene products in renal cell carcinomas

Abstract

Background. This study investigates whether or not an interrelationship exists between the expression of resistance‐related proteins (P‐glycoprotein, glutathione S‐transferase, topoisomerase II) and proto‐oncogene products (c‐fos, c‐myc, c‐K‐ras, epidermal growth factor receptor [EGF‐R], and c‐neu proteins). Methods. Thirty‐eight human renal cell carcinomas of previously untreated patients were analyzed for expression of P‐glycoprotein (P‐170), glutathione S‐transferase‐π (GST‐π), topoisomerase II (Topo II) and proto‐oncogene proteins by means of immunohistochemistry. Because of significant heterogeneity in most tumor biopsies, all analyses were done on tumor‐derived primary cell culture lines on the third or fourth passage. Results. An interrelationship between increased expression of P‐170 and GST‐π and down‐regulation of Topo II was found. Expression of the c‐fos protein was seen in 66% of the tumors; expression of the c‐myc protein, in 50%; of the c‐K‐ras protein, in 16%; of the EGF‐R protein, in 61%; and of the c‐neu protein, in 54% of the tumors. A significant correlation between the resistance factors and the c‐fos, EGF‐R, and c neu‐proteins was observed (GST/c‐fos, P=0.012; Topo II/c‐fos, P = 0.024; P‐170/EGF‐R, P < 0.001; GST/EGF‐R, P = 0.018; Topo II/EGF‐R, P = 0.027; P‐170/c‐neu, P = 0.005; GST/c‐neu, P = 0.018; Topo II/EGF‐R, P = 0.027; P‐170/c‐neu, P = 0.005; GST/c‐neu, P = 0.008; Topo II/c‐neu, P = 0.05). In contrast, interrelationships between resistance proteins and c‐myc and c‐K‐ras proteins were not found. A significant interrelationship between the investigated resistance‐related proteins or proto‐oncogene proteins and the stage or grading of the tumors was not observed. Conclusions. The results demonstrate that in renal cell carcinomas a significant relationship exists between resistance‐related proteins, such as P‐170, GST‐π, or Topo II, and proto‐oncogenes, such as c‐fos, c‐erbB1, and c‐neu. Copyright © 1993 American Cancer Society