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Serum Levels of Vascular Endothelial Growth Factor Dependent on the Stage Progression of Lung Cancer^*

^* From the Third Department of Internal Medicine (Drs. Matsuyama, Hashiguchi, Kawabata, Arimura, and Osame), Kagoshima University School of Medicine, Kagoshima City, Japan; and the Department of Respiratory Medicine (Drs. Mizoguchi and Iwami), National Minami-Kyushu Hospital, Kajiki-cho Kida, Japan.

Correspondence to: Wataru Matsuyama, MD, Third Department of Internal Medicine, Kagoshima University School of Medicine, Sakuragaoka 8–35-1, Kagoshima City 890-8520, Japan

Study objective: In lung cancer, vascular endothelial growth factor (VEGF) is an important cytokine and is correlated with tumor vessel density, malignant pleural effusions, and coagulation-fibrinolysis factors in vitro. We investigated the correlation between serum VEGF level and stage progression in lung cancer to study the predicted value of VEGF level. We also studied whether coagulation-fibrinolysis factors and PaO₂ levels, which are also important factors for the prediction of the clinical course, are correlated with VEGF.

Methods: Forty-nine patients with lung cancer were investigated prospectively. VEGF levels of sera and malignant effusions, and plasma concentrations of coagulation-fibrinolysis factors were measured by enzyme-linked immunosorbent assay. We measured PaO₂ levels in all patients at rest.

Results: Serum levels of VEGF were increased significantly according to stage progression. Additionally, plasma concentrations of D dimer, thrombin-antithrombin complex (TAT), and tissue plasminogen activator/plasminogen activator inhibitor type I complex were elevated significantly according to stage progression. The serum VEGF level had a significant positive correlation with the TAT and D dimer levels. Serum VEGF levels had a significant negative correlation with PaO₂ levels. The incidence of cerebral vascular disorder was significantly higher in the patients with systemic hypoxemia than in those without (p < 0.05). Mean VEGF levels in malignant effusions in eight patients (five with pleural effusions, two with pericardial effusions, and one with both) were extremely high, especially in pericardial effusions ([mean ± SD] pleural effusions, 531.9 ± 285.4 pg/mL; pericardial effusion, 3,071.6 ± 81.3 pg/mL).

Conclusion: We predict that in lung cancer, VEGF production and the abnormality of the coagulation-fibrinolysis system differ depending on the stage of progression of disease. Serum VEGF levels would be affected by PaO₂ levels in lung cancer.

Key Words: cerebral vascular disorder • D dimer fragments • pericardial effusion • thrombin-antithrombin complex • tissue plasminogen activator/plasminogen activator inhibitor type I complex

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