Alpha-fetoprotein-producing gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis.
OBJECTIVE
Alpha-fetoprotein (AFP)-producing gastric cancer has been associated with a poor prognosis. In the present study, the cell proliferation, apoptosis, and angiogenesis of this cancer were studied histochemically to determine its malignant potential.


METHODS
Tissue samples were taken from four patients with AFP-producing gastric cancer and 26 patients with AFP-negative gastric cancer. Cell proliferation 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 method, and the apoptotic index was determined. Angiogenesis was evaluated by measuring the microvessel density using factor VIII immunostaining, and immunostainings for vascular endothelial growth factor and thymidine phosphorylase were performed.


RESULTS
The Ki-67 LI of the AFP-producing gastric cancers was significantly higher than that of the AFP-negative gastric cancers (p < 0.01). The apoptotic index of the AFP-producing gastric cancers was significantly lower than that of the AFP-negative gastric cancers (p < 0.01). The microvessel density of the AFP-producing gastric cancers was significantly higher than that of the AFP-negative gastric cancers (p < 0.01). Vascular endothelial growth factor expression was observed in all four of the AFP-producing gastric cancers, whereas thymidine phosphorylase was not expressed in any of the AFP-producing gastric cancers.


CONCLUSIONS
These results suggest that AFP-producing gastric cancers have high malignant potential (high 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 of cancer.
Koide
N
N
Second Department of Surgery, Shinshu University School of Medicine, Asahi, Matsumoto, Japan.
Nishio
A
A
Igarashi
J
J
Kajikawa
S
S
Adachi
W
W
Amano
J
J
D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001808:Blood Vessels / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007158:Immunologic Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D013194:Staining and Labeling; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D013939:Thymidine Phosphorylase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000509:alpha-Fetoproteins / Q000096:biosynthesis*; D014841:von Willebrand Factor / Q000378:metabolism
D016228:Endothelial Growth Factors; D019394:Ki-67 Antigen; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000509:alpha-Fetoproteins; D014841:von Willebrand Factor; D013939:Thymidine Phosphorylase