Expression of vascular endothelial growth factor C correlates with lymphatic vessel density and prognosis in human gastroesophageal junction carcinoma.

BACKGROUND: The present study clarifies the clinical significance of vascular endothelial growth factor C (VEGF-C) in patients with gastroesophageal junction carcinoma treated with curative resection, as well as the correlation between VEGF-C expression and lymphatic vessel density (LVD).

PATIENTS AND METHODS: VEGF-C expression was immunohistochemically detected in 128 patients with gastroesophageal junction carcinoma, who underwent curative surgical resection. The mean optical density (MOD) was measured to represent the expression level of VEGF-C. The lymphatic vessels were labeled with D2-40 to calculate LVD. The association between MOD and LVD and clinicopathological parameters as well as the prognosis were analyzed.

RESULTS: Both VEGF-C expression and LVD were correlated with nodal metastasis and clinical stage (p < 0.05). For the high (MOD > 0.18) and low (MOD ≤ 0.18) VEGF-C group, the mean LVD was 16.9 ± 5.96 and 13.6 ± 5.58, respectively (p = 0.002), and the mean number of positive resected lymph nodes was 2.9 ± 2.44 and 2.0 ± 2.36, respectively (p = 0.025). For the high (LVD > 13) and low (LVD ≤ 13) LVD group, the mean number of positive resected lymph nodes was 3.0 ± 2.34 and 1.9 ± 2.43, respectively (p = 0.010). In univariate analysis, both high expression of VEGF-C and a high LVD level were statistically associated with poor disease-free survival (p = 0.000). Multivariate analysis showed that VEGF-C, nodal metastasis, depth of tumor invasion, postoperative chemotherapy, and resection extent were independent survival predictors (p < 0.05).

CONCLUSIONS: Increased expression of VEGF-C is correlated with high levels of LVD and poorer treatment outcome.