Markers of tumour angiogenesis and tumour cells in bone marrow in gastric cancer patients

Abstract Aims Vascular endothelial growth factors VEGF-A, VEGF-C and VEGF-D are considered to be potentially angiogenetic and lymphangiogenetic. “Minimal residual disease” is responsible for cancer progression and recurrence. In this study, we investigated the relation between expressions of VEGF-A, VEGF-C and VEGF-D in gastric cancer tissue and the presence of tumour cells in bone marrow. Methods A total of 50 resected primary gastric adenocarcinomas, 44 non-cancerous gastric mucosa and 36 lymph node metastases were analyzed by immunohistochemistry for VEGF-A, VEGF-C and VEGF-D. The specimens used were drawn from a previous study cohort, where the presence of ITC in bone marrow was confirmed with immunohistochemical assay with cytokeratin (CK)-18. Results The levels of expression of VEGF-A, VEGF-C and VEGF-D were highest in tumour ( p < 0.001), and the level in lymph node metastases was significantly higher ( p < 0.01) than in mucosa. The expression of VEGF-A was correlated significantly with venous tumour invasion ( p < 0.05) and the presence of tumour cells in bone marrow ( p < 0.05). Tumours expressing high levels of VEGF-D showed significantly advanced stages of tumour infiltration ( p < 0.05) and lymph node metastasis ( p < 0.01). Conclusions VEGF-A is a significant marker for the presence of tumour cells in the bone marrow of gastric cancer patients. Our results confirm VEGF-D as a predictor for the lymphatic spread of tumour cells. Therefore, the route of metastatic spread of gastric cancer could be determined, at least in part, by the profile of VEGF family members expressed in the primary tumour of gastric cancer patients.