Abstract

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).

Highlights

  • In an earlier study with 160 human lung tumours (Volm et al, 1990a) we demonstrated that there is a significant relationship between smoking and response to doxorubicin in vitro

  • 94 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-i (GST-i ) by means of immunohistochemistry

  • We found a significant relationship between smoking habits of the patients with NSCLC and resistance in vitro (P = 0.007) (Table V)

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Summary

Introduction

In an earlier study with 160 human lung tumours (Volm et al, 1990a) we demonstrated that there is a significant relationship between smoking and response to doxorubicin in vitro. Until now the mechanisms for the resistance of lung tumours are unknown. We have analysed non-small cell lung carcinomas (NSCLC) of previously untreated patients for the presence of P-170 and GST-i by immunohistochemistry, a method which we have found useful for detection of P-170 in the past with different human tumours (Volm et al, 1988a; Schneider et al, 1989; Bak et al, 1990). The current paper include 94 NSCLC of the earlier study (Volm et al, 1990a) because alcohol-fixed samples used for immunostaining were only collected in the second part of the study

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