Objective To observe the expression and localization of cellular homolog FLICE-like inhibitory protein (c-FLIP) in the procedure of benign biliary stricture formation and discuss the significances. Methods The method of in situ hybridization was used in anastomotic tissues from 15 dogs (experimental group) in 2, 3, 4, 5, 6 months after bile duct injury and 15 matching sham operation dogs (sham operation group) for analyzing the expression and localization of c-FLIP and calculating the average integrated optical density of each slice. Stain cells were counted under the magnification field (×400) and at least 5 fields per slice were examined. The cells stained red in the nuclei and (or) the cytoplasm were positive cells. The signals meant: Negative for cells no stained, weak positive for the cells with nuclei and (or) cytoplasm stained pink; b positive for the cells stained the bright red; while middle positive for the cells stained between the both. The image analysis software （Image pro plus 4.5） was applied in the gland tissue and interstitial tissue in each slice to calculate the average integrated optical density for the expression of c-FLIP. Results In the experimental group, there were all b positive expressions of c-FLIP in the interstitial tissue at all the time points, mainly expressed in the cytoplasm of fibroblast and very little or almost no expression in the glandular tissue. Positive expression of c-FLIP in the interstitial tissue was significantly ber than that of gland tissue (Plt;0.05); There were no significant differences among each time point in either the interstitial tissue or gland tissue (Pgt;0.05). In the sham operation group, there were all weak positive expressions of c-FLIP in the interstitial tissue and gland tissue at all the time points and was no significant difference (Pgt;0.05), no difference between each phase (Pgt;0.05). The expression of c-FLIP in the experimental group was significantly higher than that in the sham operation group in the interstitial tissue at all the time (Plt;0.05), while no significant that in the gland tissue (Pgt;0.05). Conclusion After bile duct injury, the expression of c-FLIP in anastomotic interstitial tissue is sustainable, by which the continuing obstruction effect to apoptosis may have a close relationship with the formation of biliary benign stricture.
Objective To investigate the prevalence of cellular FLICE-like inhibitory protein (cFLIP) alterations in colorectal cancer and their possible implications for the progression of colorectal cancer. Methods The long type cFLIP (cFLIPL) was examined in 43 colorectal cancer specimens and the matched normal colorectal specimens by immunohistochemistry. Immunohistochemical staining for cFLIPL was assessed on an arbitrary semi-quantitative scoring system. Stained cells were counted under the magnification field (×100) and at least 20 fields per case were examined. Fields with non-stained cells were scored 0; fields with stained cells less than 5% were scored 1; fields with stained cells from 5% to 25% were scored 2; fields with stained cells between 26% and 50% were scored 3; and fields with stained cells more than 50% were scored 4. According to the above schedule， a mean score of each specimen was calculated. Results cFLIPL protein expressions of variable intensity and extent were detected in the normal colorectal mucosa and adenocarcinomas. cFLIPL was mainly expressed in the cytoplasma. The positive cells were distributed in diffuse manner. The mean expression score in normal mucosa ranged from 0 to 2.95 (mean score: 1.55±0.86); 4.7%(2/43) of all cases were unstained and 20.9%(9/43) showed a weakly stained pattern (0＜mean score≤1); 74.4%(32/43) of all cases were positively stained (1.00＜mean score≤2.95), respectively. cFLIPLprotein was expressed in all adenocarcinomas and the score ranged from 0.80-4.00 (mean score: 3.06±0.75); 62.8% (27/43) of the tumors examined were predominantly cFLIPL positive (mean score ＞3), 34.9%(15/43) of the tumors were cFLIPLpositive (1＜mean score ≤3) and only one case was cFLIPL weakly positive (score: 0.80). 72.1% (31/43) of adenocarcinomas expressed cFLIPLmore intensely and extensively than matched normal colonic mucosa. cFLIPL expression of colorectal cancer was significantly higher than that of matched normal mucosa, which was statistically significant (P＜0.01). The extent of cFLIPL expression in tumors was independent of Dukes stage, tumor stage, gross type of tumor, histological type, or lymph and hepatic metastasis. Conclusion The expression level of cFLIPL in adenocarcinomas is much higher than that in matched normal mucosa. Overexpression of cFLIPL is a tumor-specific phenomenon, which can provide a selective growth advantage for colorectal cancer cells to escape from death receptor-mediated apoptosis.