Detection of the multidrug resistance marker P-glycoprotein by immunohistochemistry in malignant lung tumours

Abstract

Background - The multidrug resistance marker P-glycoprotein (P-gp) was studied immunohistochemically in 78 primary malignant lung tumours. P-gp is a 170 kD transmembrane ATP dependent drug efflux pump which has been shown to be important in the resistance of some tumours to chemotherapy. Certain normal tissues express P-gp and tumours derived from these tissues are often insensitive to cytotoxic agents, showing raised P-gp levels innately or following chemotherapy or radiotherapy. Methods - Samples from 78 patients undergoing surgery for primary malignant lung tumours were snap frozen and stained immunohistochemically using the monoclonal antibody C219 which reacts with a P-gp epitope. None of the study group had received chemotherapy or radiotherapy before surgery was performed. Results - Twenty seven of the 78 lung tumours (34.6%) showed immunohistochemically detectable levels of P-gp which varied with tumour type; 17 of 54 squamous cell carcinomas (31.5%), seven of 15 adenocarcinomas (46.7%), and neither of two small cell carcinomas showing positive staining. In six of seven cases normal respiratory epithelium present showed the presence of P-gp. Conclusions - P-gp is immunohistochemically detectable in frozen tissue from a proportion of malignant lung tumours before exposure to radiotherapy or drugs associated with multidrug resistance. It may have a role in tumour resistance to cytotoxic drugs, but further clinical studies will be required to evaluate any correlation between P-gp levels and response to treatment.