alpha-fetoprotein-producing gastric cancer: Histochemical analysis of cellproliferation, apoptosis, and angiogenesis

OBJECTIVE: alpha-Fetoprotein (AFP)-producing gastric cancer has been associ ated with a poor prognosis. In the present study, the cell proliferation, a poptosis, and angiogenesis of this cancer were studied histochemically to d etermine its malignant potential. METHODS: Tissue samples were taken from four patients with AFP-producing ga stric cancer and 26 patients with AFP-negative gastric cancer. Cell prolife ration was evaluated by Ki-67 immunostaining, and the Ki-67 labeling index (LI) was determined. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling me thod, and the apoptotic index was determined. Angiogenesis was evaluated by measuring the microvessel density using factor VIII immunostaining, and im munostainings for vascular endothelial growth factor and thymidine phosphor ylase were performed. RESULTS: The Ki-67 LI of the AEP-producing gastric cancers was significantl y higher than that of the AFP-negative gastric cancers (p < 0.01). The apop totic index of the AFP-producing gastric cancers was significantly lower th an that of the AFP-negative gastric cancers (p < 0.01). The microvessel den sity of the AFP-producing gastric cancers was significantly higher than tha t of the AFP-negative gastric cancers (p < 0.01). Vascular endothelial grow th factor expression was observed in all four of the AFP-producing gastric cancers, whereas thymidine phosphorylase was not expressed in any of the AF P-producing gastric cancers. CONCLUSIONS: These results suggest that AFP-producing gastric cancers have high malignant potential thigh proliferative activity, weak apoptosis, and rich neovascularization) compared with that of AFP-negative gastric cancers . These biological characteristics of AFP-producing gastric cancer reflect the aggressive behavior and the poor prognosis of patients with this type o f cancer. (Am J Gastroenterol 1999;94:1658-1663. (C) 1999 by Am. Cell. of G astroenterology).