Preoperative Serum Vascular Endothelial Growth Factor-C (VEGF-C) Levels Predict Recurrence in Patients with Esophageal Cancer

Background: Circulating vascular endothelial growth factor-C (VEGF-C) levels were measured in patients with esophageal cancer to assess the value of VEGF-C as a biomarker for predicting tumor recurrence. Patients and Methods: Preoperative serum samples were acquired from 80 patients and healthy volunteers who served as normal controls. VEGF-C levels were assessed using enzyme-linked immunosorbent assay (ELISA). Results: The preoperative serum VEGF-C level in patients with esophageal cancer was significantly higher than in healthy volunteers. Furthermore, patients with recurrence had significantly higher preoperative serum VEGF-C levels than patients without recurrence, and a high preoperative serum VEGF-C level was found to be an independent risk factor for recurrence, in addition to lymph node metastasis. Conclusion: Preoperative VEGF-C levels may reflect malignancy, such as lymph node metastasis, and predict recurrence in patients with esophageal cancer. Therefore, the preoperative VEGF-C level may be a useful biomarker for choice of multimodality therapy. Lymphatic vessels play an important role in the maintenance of tissue homeostasis (1) and transport of immune cells (2), and also serve as the primary conduit for malignant tumor cell metastasis to regional lymph nodes (3). Lymph node metastasis is a characteristic of malignant cancers and is observed more frequently in esophageal cancer than in other digestive tract cancers, making it one of the most important prognostic factors (4). Since the induction of tumor lymphangiogenesis by vascular endothelial growth factor (VEGF)-C or -D was first reported to promote cancer metastasis (3, 5), many investigations have shown that tumor expression of lymphangiogenesis factors is correlated with clinico-pathological features (especially metastatic tumor spread) and prognosis in various human cancers (6). VEGF-C expression in tumor or stromal cells has been directly correlated with clinicopathological features, including lymph node metastasis in human esophageal squamous cell carcinoma (7). Kimura et al. reported that tumor expression of VEGF-C is correlated with lymphatic involvement and prognosis in esophageal squamous cell carcinoma (8), and Ishikawa et al. suggested that VEGF-C might play a positive role in the early stage of esophageal carcinogenesis based on the active production of VEGF-C in some dysplastic lesions, as well as in esophageal carcinomas (9). However, serum VEGF-C levels in patients with esophageal cancer have not been measured. Therefore, we examined the association of VEGF-C with clinicopathological features in patients with esophageal cancer and assessed the serum VEGF-C level as a predictor of recurrence.