Differential expression of vascular endothelial growth factor-A, -C and -D for the diagnosis and prognosis of cancer patients with malignant effusions.

Elevated levels of vascular endothelial growth factor (VEGF) contribute to angiogenesis and serous cavity effusions. The present study evaluated the diagnostic and prognostic values of VEGF-A, -C and -D proteins in the serum, supernatant fluid and exfoliated cells of cancer patients with malignant effusions compared with patients with benign effusions. An enzyme-linked immunosorbent assay was used to detect levels of VEGF-A, -C and -D proteins in the sera of 79 cases (30 lung cancer, 21 gastric cancer and 28 benign effusions) and the supernatant fluid of 96 cases (38 lung cancer, 30 gastric cancer, and 28 benign effusion). Immunocytochemistry detected the expression of VEGF-A, -C and -D proteins in effusion cells from 71 cases (34 lung cancer, 17 gastric cancer and 20 benign effusions). The data were further investigated to determine whether there was an association between VEGF subtype expression and clinicopathological characteristics and prognosis. The expression levels of VEGF-A in the supernatant fluid were increased in the lung and gastric cancer patient samples compared with the benign effusions (P<0.05). The VEGF-A level in the supernatant fluid was significantly increased compared with the corresponding sera of patients with malignant effusion (P<0.05). VEGF-A, -C and -D proteins in the exfoliated cells from primary lung or gastric cancer effusions were expressed at 52.94, 70.58 and 82.35%, respectively, whereas their expression was not detected in the exfoliated cells from benign effusion, with the exception of mesothelial cells. The levels of VEGF-A and VEGF-C in the supernatant fluid levels and the cell levels of VEGF-A were inversely associated with age; in addition, VEGF-A levels in the supernatant fluid were associated with malignant and bloody effusion, and only cavity metastasis (P<0.05). Survival analysis demonstrated a relatively reduced survival time for patients with VEGF-A levels of >406.19 pg/ml in the supernatant fluid compared with patients with VEGF-A levels of ≤406.19 pg/ml (P=0.066). Serum VEGF-A, -C and -D levels exhibited no evident clinical significance in the diagnosis and prognosis of serous cavity effusions. VEGF-A in the supernatant fluid merits further study as a tumor marker in the clinical setting to discriminate benign from malignant effusions, while cellular VEGF-C and -D may contribute to the formation of malignant effusions.