Angiogenic growth factors and their receptors in non-small cell lung carcinomas and their relationships to drug response in vitro.

Tumor specimens of non-small cell lung carcinomas (NSCLC) from previously untreated patients (n = 153) were analysed immunohistochemically for expression of vascular endothelial growth factor (VEGF), VEGF-receptor (Flt-1), basic fibroblast growth factor (bFGF) and FGF-receptor (FGFR-1, (Flg). Expression of the proteins was compared with the in vitro response of the tumors against doxorubicin. The data clearly demonstrate that a significant relationship exists between VEGF (p < 0.001) and Flt-1 expression (p < 0.01) and drug response. The expression of VEGF and Flt-1 was lower in resistant than in sensitive tumors. In contrast, no significant interrelationship was found between expression of bFGF and response to doxorubicin. However, there exists a significant correlation between the expression of FGF-receptor (FGFR-1) and the response of the carcinomas to doxorubicin (p < 0.05). Expression of FGFR-1 was more frequently negative or weak in resistant and more frequently moderate or high in sensitive NSCLC. The data from this investigation clearly demonstrate that a significant interrelationship exists between the expression of VEGF, VEGF-receptor Flt-1 and FGF-receptor, FGFR-1 and the response of NSCLC to doxorubicin in vitro.