Distinct roles of VEGF-A and VEGF-C in tumour metastasis of gastric carcinoma

The expression of VEGF-A and -C was investigated immunohistochemically in 51 specimens of gastric carcinoma. The expression intensity was evaluated by means of a semiquantitative scoring system and a quantitative analysis. The results showed that VEGF-A and -C were located mainly in the cytoplasm of tumour cells: 68.6% (34/51) and 62.8% (32/51) positive for VEGF-A and VEGF-C. VEGF-C expression was more frequent in tumours of the deceased patients [88.2% (15/17)] compared to that in the survivors [47.0% (16/34)]. Quantitative VEGF-C levels in the deceased patients were 0.304 +/- 0.023, which was significantly elevated compared to that in the survivors (0.131 +/- 0.018) (p < 0.01). The frequency of VEGF-C expression was higher in patients with lymph node metastases (80.0%, 28/35) compared to those with negative nodes (25%, 4/16). Accordingly, its levels were markedly elevated in the former (0.230 +/- 0.017) than in the latter (0.089 +/- 0.011) (p < 0.01). Furthermore, tumour cell invasion into the enlarged lymphatic vessels was also associated with VEGF-C expression. Its expression levels were 0.271 +/- 0.028 in lymph vessel invasion and 0.153 +/- 0.021 in the absence of invasion (p < 0.01). VEGF-A expression, although correlated with survival, distant metastasis, ascites formation, and blood vessel invasion, was not associate with lymph node metastasis, lymphatic vessel invasion. The expression levels of the two factors were inversely correlated with overall survival rates. It can be conclude that VEGF-C expression in tumour tissues is indicative of lymphatic metastasis, whereas VEGF-A expression is more likely to be associated with haematogenous metastasis. Both VEGF-A and -C could serve as a prognostic biomarker in patients with gastric carcinoma.