Angiogenesis of AFP producing gastric carcinoma: correlation with frequent liver metastasis and its inhibition by anti-AFP antibody.

We studied roles of angiogenesis in patients with alpha-fetoprotein (AFP)-producing gastric carcinoma (APGC), which is well known to have a poor prognosis and frequent liver metastases. Immunohistochemical analyses were conducted using antibodies against alpha-fetoprotein, factor VIII (endothelial cells) and vascular endothelial growth factor (VEGF). Archival specimens of APGC (n=25) and non-APGC (n=68) were studied. Expressions of vessel density and VEGF were significantly higher in APGC than those in non-APGC (p<0.001). There is a correlation among the AFP expression, the vessel density and the VEGF expression in APGC (p<0.001). Next, we studied the effects of anti-AFP antibody on APGC xenotransplanted in nude mice. There is significant inhibition of tumor growth in the treatment groups compared to the control groups in 2 APGC lines (p<0.01). There were also significant differences in serum AFP and VEGF levels between treatment groups and non-treatment groups in 2 APGC lines, but not in a non-APGC line. Moreover, vessel densities of the treatment groups were significantly lower than those of the control groups in the two lines. These findings thus suggest that the biological behavior of APGC is angiogenesis-dependent. Down-regulation of angiogenesis by anti-AFP antibody suggest that AFP itself may up-regulate angiogenesis, and the treatment by antibody could have anti-angiogenic effects, inhibiting metastasis, especially liver metastasis in APGC.