Background: Hematogenous metastasis occurs when cancer cells released from the primary site enter blood vessels and are transported to distant organs, where they attach and proliferate. Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells.
Methods: We analyzed data on 1184 Japanese adult men and women with gastric cancer with respect to the relation between vascular invasion and the potential for tumor angiogenesis and metastasis. All these patients were treated from 1976 to 1995 in the Department of Surgery II, Kyushu University. In 300 patients, the expression of vascular endothelial growth factor (VEGF) and p53 protein in tumor tissues was examined by using an immunohistochemical staining method or Northern blotting or both. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody.
Results: Vascular invasion was evident in 254 patients (21.5%), and in these patients lymphatic invasion was more frequent and the rate of lymph node metastasis was higher in relation to the extent of vascular invasion. The positive findings were directly related to the depth of invasion and the presence of lymph node and liver metastasis. Tumor invasive and metastatic rates increased in relation to the extent of vascular invasion. Expressions of VEGF and p53 protein were higher and microvessel density was more prominent in tumor tissues in relation to the extent of vascular invasion. A close relation between VEGF and p53 protein expressions was also noted in tumors that showed vascular invasion. The expression of VEGF is one of the independent risk factors for vascular invasion. The postoperative outcome was poorer in patients with vascular invasion in relation to the extent of vascular invasion.
Conclusions: Our findings show that gastric cancers with characteristics of vascular invasion have greater intratumoral angiogenesis and that VEGF and p53 overexpression is associated with intratumoral angiogenesis and metastases to distant organs.