Prognostic significance of Fas and Fas ligand system-associated apoptosis in gastric cancer.
BACKGROUND
Previous studies indicate that gastric carcinomas express Fas ligand and down-regulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated.


METHODS
Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method.


RESULTS
The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD8+ cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients' age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD8+ cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors.


CONCLUSIONS
Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD8 + cells.
Ohno
S
S
Second Department of Surgery, Shimane Medical University, Izumo, Japan. satoshio@shimane-med.ac.jp
Tachibana
M
M
Shibakita
M
M
Dhar
D K
DK
Yoshimura
H
H
Kinugasa
S
S
Kubota
H
H
Masunaga
R
R
Nagasue
N
N
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017209:Apoptosis; D016827:CD8 Antigens / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D015588:Observer Variation; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D019014:fas Receptor / Q000378:metabolism*
D016827:CD8 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor