Association of serum vascular endothelial growth factor-C and lymphatic vessel density with lymph node metastasis and prognosis of patients with gastric cancer

Abstract

Aim: To investigate whether serum vascular endothelial growth factor-C (SVEGF-C), VEGF-C, and lymphatic vessel density (LVD) in tumor tissues are related to lymph node metastasis (LNM) and prognosis in gastric cancer.

Methods: SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients.

Results: The SVEGF-C level in gastric cancer patients (595.9 +/- 201.0 ng/L) was significantly higher (P = 0.000) than controls (360.0 +/- 97.4 ng/L). Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups III and IV (P = 0.000). The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively (cut-off = 542.5 ng/L). The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues (65% vs 20%; P = 0.001). VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage (P = 0.000). LVD was 10.7 +/- 3.1/200 HP in the experimental group vs 4.9 +/- 1.3/200 HP in controls (P = 0.000); LVD in cancerous tissues with and without LNM was 12.0 +/- 2.7/200 HP vs 7.6 +/- 0.5/200 HP, respectively (P = 0.000). SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients (P = 0.000); SVEGF-C level was related to LVD (P = 0.000). Kaplan-Meier survival analysis factors predicating poor prognosis were: SVEGF-C level (P = 0.001), VEGF-C expression and LVD (both P = 0.000).

Conclusion: SVEGF-C level, VEGF-C and LVD are related to LNM and poor prognosis of patients with gastric cancer. SVEGF-C may be a biomarker for LNM in gastric cancer.

Figures

Figure 1

VEGF-C (A) and podoplanin (B) expression in gastric cancer (S-P, × 200).

Figure 2

Kaplan-Meier survival curves in gastric cancer SVEGF-C, LVD and VEGF-C groups. A: SVEGF-C; B: LVD; C: VEGF-C.