Action and mechanism of Fas and Fas ligand in immune escape of gallbladder carcinoma.
OBJECTIVE
To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape.


METHODS
Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues, 18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder carcinoma.


RESULTS
The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (chi(2) = 4.89, P<0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t' = 4.19, P<0.01) and chronic cholecystitis (t' = 8.06, P<0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin I-III carcinoma than that in poorly-differentiated carcinoma (t' = 2.63, P<0.05) and Nevin IV-V carcinoma (t' = 3.33, P<0.01). The confidence interval (CI) of infiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin I-III carcinoma was very significantly lower than that in carcinoma (t' = 6.99, P<0.01), adenoma (t' = 3.66, P<0.01), poorly-differentiated carcinoma (t' = 5.31, P<0.01) and Nevin IV-V carcinoma (t' = 3.76, P<0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P<0.05), and was not significantly lower in Nevin I-III carcinoma than in Nevin IV-V carcinoma (t = 1.42, P>0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis.


CONCLUSIONS
FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.
Xu
Li-Ning
LN
Department of General Surgery of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
Zou
Sheng-Quan
SQ
Wang
Jian-Ming
JM
D000236:Adenoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002764:Cholecystitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D005706:Gallbladder Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology* / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor