Soluble vascular endothelial growth factor levels in lung cancer. Relationship with coagulation and platelet activation.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor essential for tumor growth and metastasis. Lately, it was shown that thrombin activation of platelets causes VEGF release, and that VEGF-stimulated endothelial cells promote adhesion and activation of platelets through the generation of thrombin. Therefore, the present study was aimed to analyze plasma soluble (s)VEGF levels in 65 patients with non-small cell lung cancer (NSCLC)[32 adenocarcinomas (ADC), 33 squamous cancer (SC)] and 33 age- and sex-matched healthy donors. Furthermore, a correlation analysis between sVEGF and markers of platelet activation (sP-selectin) or thrombin generation [thrombinantithrombin complexes (TAT)] was performed to test the hypothesis of a role of haemostatic abnormalities in tumor growth and metastatization in NSCLC. Median plasma sVEGF levels were higher in NSCLC (68.2 pg/ml) compared to controls (28.6 pg/ml; p<0.005). Similarly, sP-selectin (55.5 vs. 48.8 ng/ml, p<0.05) and TAT (9.6 vs. 2.1μg/l, p<0.001) were higher in NSCLC than controls. Median sVEGF (F=6.3, p<0.005) and sP-selectin (F=3.7, p<0.03) levels were higher in SC than either ADC or controls. A correlation analysis among the variables showed that sVEGF correlated with sP-selectin (r=0.57, p<0.001) and TAT (r=0.52, p<0.005) only in SC. sP-selectin correlated with TAT complexes (r=0.39, p<0.05) in the same histotype. Multiple regression analysis including age, sex, diagnosis, sVEGF, sP-selectin and TAT revealed that sP-selectin (beta=0.41, p<0.002), TAT (beta=0.34, p<0.02), and SC (beta=0.22, p<0.05) were independently related to sVEGF. In particular, mean sP-selectin and TAT levels were approximately 2-fold higher in SC patients with sVEGF levels above the median value. These results suggest that haemostatic abnormalities are strictly related to the presence of elevated sVEGF levels in patients with lung SC.