Overexpression of P-glycoprotein and glutathione S-transferase-pi in resistant non-small cell lung carcinomas of smokers.
Ninety-four human non-small cell lung carcinomas (NSCLC) of previously untreated patients were analysed for the presence of P-glycoprotein (P-170) and glutathione S-transferase-pi (GST-pi) by means of immunohistochemistry. The expression of P-170 and GST-pi was compared with the results of doxorubicin resistance of the tumours in vitro and the smoking habits of the patients. A significant relationship between smoking habits of the patients and resistance of NSCLC was found (P = 0.007). Of the 72 tumours of smokers 57 (= 79%) were resistant, whereas of the 22 tumours of non-smokers only 11 (= 50%) showed resistance. Identical results were obtained when the analysis was restricted to patients with epidermoid lung carcinomas (P = 0.004). In contrast to these data, there exists no relationship between resistance and smoking for adenocarcinomas of the lung. Forty-two (= 58%) out of the 72 NSCLC of smokers expressed P-170, whereas out of 22 tumours of non-smokers only two tumours (= 9%) showed P-170 expression (P less than 0.0001). Similar results were obtained with epidermoid carcinomas (P = 0.004) and adenocarcinomas (P = 0.027). Fifty (= 69%) of 72 NSCLC of smokers revealed expression of GST-pi, whereas only nine (= 41%) of 22 tumours of non-smokers showed GST-pi expression (P = 0.015). Significant correlations also exist between resistance in vitro and expression of P-170 (P less than 0.0001) or expression of GST-pi (P less than 0.0001). Furthermore, a significant relationship between both proteins could be demonstrated (P less than 0.0001).
Volm
M
M
German Cancer Research Center, Institute of Experimental Pathology, Heidelberg.
Mattern
J
J
Samsel
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000230:Adenocarcinoma / Q000737:chemistry; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry*; D004351:Drug Resistance; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D012907:Smoking / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D005982:Glutathione Transferase