Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by host and/or tumor cells. The role of angiogenesis and angiogenic factor expression in intestinal- and diffuse-type gastric cancer are undefined. Archival specimens of 51 intestinal-type and 38 diffuse-type human gastric carcinomas were examined for tumor vessel counts, angiogenic factor expression, and the presence or absence of angiogenic factor receptors on tumor endothelium using

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... ntibodies against vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1), basic fibroblast growth factor (bFGF) and its receptors (bek and flg), and factor VIII (endothelial cells). Vessel count and VEGF and bFGF expression were higher in intestinal-type than in diffuse-type gastric cancers (P = 0.01, P < 0.001, and P < 0.001, respectively). Similarly, vessel count and VEGF expression were higher in patients with liver metastasis than in patients with peritoneal dissemination (P = 0.003 and P = 0.01, respectively). Vessel count correlated with VEGF expression and the presence of endothelial KDR in intestinal-type gastric cancer (P = 0.003 and P = 0.02, respectively) but not diffuse-type gastric cancer. Vessel count, VEGF expression, and presence of endothelial KDR increased with increasing stage of disease in intestinal-type gastric cancer but not diffuse-type gastric cancer. The expression of bFGF and its receptors did not correlate with vessel count in either cancer type. These findings suggest that the pattern of metastasis in intestinal-type gastric cancer is angiogenesis dependent. The correlation of VEGF expression and its endothelial receptor with vessel count and stage of disease suggests that VEGF is at least one of the factors responsible for the induction of angiogenesis in intestinal-type gastric cancer.