Objective: Lymph node metastasis is a characteristic of malignant cancers and is observed more frequently in oesophageal cancer than in other digestive tract cancers, making it one of the most important prognostic factors. Vascular endothelial growth factors C (VEGF-C) and D (VEGF-D) are important lymphangiogenic factors in human cancers and lymphangiogenesis is associated with lymph node metastasis. The aim of the study was to determine the correlation between pre-treatment serum levels of VEGF-C (sVEGF-C) and VEGF-D (sVEGF-D) and clinicopathologic features in patients with oesophageal cancer.
Methods: Serum VEGF-C and sVEGF-D were measured by enzyme-linked immunoadsorbent assay (ELISA) on 149 patients with oesophageal cancer, 29 patients with benign oesophageal diseases and 30 healthy controls.
Results: Serum VEGF-C and sVEGF-D levels were significantly higher in patients with oesophageal carcinoma than in the control group (p<0.001 and p=0.001, respectively) or in the benign oesophageal diseases group (p=0.04 and p=0.03, respectively). Subgroup analysis showed that lymph node metastasis (p=0.001), stage (p=0.001), tumour depth (p=0.006), resectability (p=0.002), tumour size (p=0.01), distant metastases (p=0.01) and histological grading (p=0.04) were correlated with an elevated level of sVEGF-C. Elevated levels of sVEGF-D were associated with tumour depth (p=0.002), stage (p=0.01) and lymph node metastasis (p=0.02). Among the patients (n=83) who underwent potentially curative surgery, the overall survival time (p=0.008) was shorter for patients with a high level (>8667 pg ml(-1)) of sVEGF-C than for those with a low level (<8667 pg ml(-1)), when the cut-off value was determined on the basis of the median value in oesophageal cancer patients. On univariate regression analysis, tumour size, tumour depth, stage, lymph node metastases, distant metastases, resectability and sVEGF-C were found to be significant prognostic factors.
Conclusions: These results suggest that pre-treatment levels of sVEGF-C and sVEGF-D reflect lymph node metastases and advanced stage of oesophageal cancer. Serum VEGF-C may be useful in predicting poor outcome for patients undergoing a potentially curative oesophagectomy.
Copyright 2010. Published by Elsevier B.V.