Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma

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 gro wth and metastasis and depends on the production of angiogenic factors by t umor 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 pote ntial for tumor angiogenesis and metastasis. All these patients were treate d from 1976 to 1995 in the Department of Surgery II, Kyushu University. In 300 patients, the expression of vascular endothelial growth factor (VEGF) a nd p53 protein in tumor tissues was examined by using an immunohistochemica l staining method or Northern blotting or both. Intratumoral microvessels w ere stained with anti-CD31 monoclonal antibody. Results. Vascular invasion was evident in 254 patients (21.5%), and in thes e patients lymphatic invasion was more frequent and the rate of lymph node metastasis was higher in relation to the extent of vascular invasion. The p ositive findings were directly related to the depth of invasion and the pre sence of lymph node and liver metastasis. Tumor invasive and metastatic rat es increased in relation to the extent of vascular invasion. Expressions of VEGF and p53 protein were higher and microvessel density was more prominen t 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 indepen dent risk factors for vascular invasion. The postoperative outcome was poor er 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 metast ases to distant organs.