The association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor.

Abstract Although tumors metastasize to lymph nodes via the lymphatics, the importance of vascular endothelial growth factor-C (VEGF-C) expression in mediating the process has not been well elucidated. We investigated the correlation between VEGF-C expression and lymphatic vessel density (LVD) and node metastasis in cases with gastric cancer and gastrointestinal stromal tumor (GIST). Immunohistochemistry, VEGF-C expression and LVD were performed in 41 patients with gastric cancer invading the muscularis propria and 19 patients with GIST. The clinicopathological features of these cases were compared. In gastric cancer, VEGF-C expression was significantly associated with tumor LVD and lymph node metastasis. In GIST, none of these patients had lymph node metastasis and VEGF-C expression was not detected. The LVD was significantly higher in the cases with gastric cancer than in those with GIST. In gastric cancer, LVD was increased more in patients with positive lymph nodes than in those with negative lymph nodes. These results indicate that the expression of VEGF-C is associated with tumor LVD and lymph node metastasis, suggesting that VEGF-C plays a critical role in node metastasis via lymphangiogenesis. The clinical observation that GIST rarely metastasizes to the lymph nodes may depend on the lack of VEGF-C expression.