Expression of Fas and Fas ligand in human gastric adenomas and intestinal-type carcinomas: correlation with proliferation and apoptosis.
BACKGROUND
Fas (APO-1/CD95), a member of the tumor necrosis factor/nerve growth factor receptor superfamily, mediates apoptosis in response to agonistic antibodies or Fas ligand (FasL) binding. Previous reports indicated an up-regulation of FasL in gastric carcinomas to evade host immune attack. Fas/FasL expression, however, has not been analyzed in terms of apoptosis and proliferation in gastric adenoma and carcinoma.


METHODS
This study was conducted on seven human gastric carcinoma cell lines, 47 gastric adenomas, and 75 intestinal-type adenocarcinomas (48 early and 27 advanced carcinomas). Fas/FasL expression was examined by immunohistochemistry, apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method, and Fas gene mutation by a reverse transcriptase (RT) polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing method.


RESULTS
Fas and FasL expressions were noted in 18 (38.3%) and 17 (36.2%) adenomas, in 21 (43.8%) and 33 (68.8%) early carcinomas, and in 10 (37.0%) and 19 (70.4%) advanced carcinomas, respectively. The frequency of FasL expression was significantly higher in advanced carcinomas than in the early carcinomas and adenomas; in contrast, there was no significant difference in Fas expression among the three groups. The mean apoptotic index (AI) was 4.96+/-0.51 in the adenomas, 2.96+/-0.23 in the early carcinomas, and 1.67+/-0.17 in the advanced carcinomas. A significantly higher Al was noted in the lesions with Fas expression than in those without Fas expression in all three groups. No missense mutations of the Fas gene were detected in any of the gastric carcinoma cell lines, or in the gastric adenomas or carcinomas.


CONCLUSIONS
Upregulation of FasL may correlate with the progression of gastric carcinoma. Apoptosis in gastric adenoma and carcinoma cells may occur via Fas-dependent and -independent pathways, but further clarification is needed.
Osaki
M
M
First Department of Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Kase
S
S
Kodani
I
I
Watanabe
M
M
Adachi
H
H
Ito
H
H
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D004591:Electrophoresis, Polyacrylamide Gel; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor