Expression of Fas and Fas ligand in human gastric adenomas and intestinal-type carcinomas: Correlation with proliferation and apoptosis

Gastric Cancer (Impact Factor: 3.72). 11/2001; 4(4):198-205. DOI: 10.1007/s10120-001-8010-z


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 upregulation 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 AI 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.

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