Expression of c-FLIP in Gastric Cancer and its Relation to Tumor Cell Proliferation and Apoptosis

BACKGROUND The expression of c-FLIP (cellular Fas-associated death domain-like interleukin-1 beta-converting enzyme (FLICE)-inhibitory protein), which is a member of the family of inhibitors of apoptosis, has been associated with tumor development and progression. The aim of this study was to evaluate the expression of c-FLIP in gastric cancer and its correlation with tumor cell proliferation, apoptosis and the clinicopathologic features. METHODS Immunohistochemical staining with anti-c-FLIP antibody was performed in 98 tissue samples obtained from gastric cancer patients who underwent surgical treatment. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), and the proliferative cells were visualized by staining with Ki-67 antibody. RESULTS The positive expression of c-FLIP in the gastric cancer tissues was demonstrated in 57.1% of the cases. The expression of c-FLIP was increased in the gastric cancer tissues compared with the matched normal gastric mucosa. The expression of c-FLIP was significantly associated with histologic differentiation (p = 0.038). However, there was no association between the c-FLIP expression and the other clinicopathological parameters, including patient survival. The Ki-67 labeling index (KI) for the 98 tumors ranged from 7.6 to 85.0 with a mean KI of 50.4 +/- 15.7. The mean KI value of the c-FLIP positive tumors was 54.1 +/- 15.3 and this was significantly higher than that of the c-FLIP negative tumors (p = 0.005). The apoptotic index (AI) for the 98 tumors ranged from 0.0 to 10.0 with a mean AI of 7.4 +/- 2.3. There was no significant difference between the c-FLIP expression and the AI (p = 0.347). CONCLUSIONS These results suggest that the c-FLIP expression may be associated with tumor cell proliferation of gastric cancer.