356

FASLG

Fas ligand (TNF superfamily, member 6);FASLG;Fas ligand (TNF superfamily, member 6)

CD95 ligand|apoptosis (APO-1) antigen ligand 1|apoptosis antigen ligand|fas antigen ligand|tumor necrosis factor ligand superfamily member 6

1q23

protein-coding

BACKGROUND AND AIM: Our purpose is to study the clinical significance of Fas/FasL expression in colon cancer and liver metastases (LM). MATERIAL AND METHODS: The expression of Fas/FasL in 68 patients with colon cancer was examined immunohistochemically and correlated to the clinicopathological features of the tumors. RESULTS: High expression of FasL, was observed in stage D and in LM (p=0.024). Fas expression was reduced in stage D tumors and in LM, when compared to earlier stages of disease (p=0.024). LM had also shown a decreased expression of Fas (p=0.016). tumors with low FasL expression upregulate more often their Fas expression (p = 0.028). No correlation could be established regarding the patients survival. CONCLUSIONS: Low expression of Fas and high expression of FasL are more often in colon tumor stage D and in liver metastasis; these imply tumor aggression, resistance against apoptosis, and could be held as negative prognostic factors.

AIM: 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

AIM: To study the role of Fas ligand (FasL) and Caspase-3 expression in carcinogenesis and progression of gastric cancer and molecular mechanisms of relevant immune escape. METHODS: FasL and Caspase-3 expression was studied in adjacent epithelial cells, cancer cells and lymphocytes of primary foci, and cancer cells of metastatic foci from 113 cases of gastric cancer by streptavidin-biotin-peroxidase (S-P) immunohistochemistry. expression of both proteins in cancer cells of primary foci was compared with clinicopathological features of gastric cancer. The relationship between FasL expression in cancer cells and Caspase-3 expression in cancer cells or infiltrating lymphocytes of primary foci was investigated. RESULTS: cancer cells of primary foci expressed FasL in 53.98 % (61/113) of gastric cancers, more than their adjacent epithelial cells (34.51 %, 39/113) (P=0.003, chi(2)=8.681), while the expression of Caspase-3 in cancer cells of primary foci was detected in 32.74 % (37/113) of gastric cancers, less than in the adjacent epithelial cells (50.44 %, 57/113) (P=0.007, chi(2)=7.286). Infiltrating lymphocytes of the primary foci showed positive immunoreactivity to Caspase-3 in 70.80 % (80/113) of gastric cancers, more than their corresponding adjacent epithelial cells (P=0.001, chi(2)=10.635) or cancer cells of primary foci (P=0.000, chi(2)=32.767). FasL was less expressed in cancer cells of metastases (51.16 %, 22/43) than in those of the corresponding primary foci (81.58 %, 31/38) (P=0.003, chi(2)=9.907). Conversely, Caspase-3 was more expressed in cancer cells of metastases (58.14 %, 25/43) than in those of the corresponding primary foci (34.21 %, 13/38) (P=0.031, chi(2)=4.638). FasL expression was significantly correlated with tumor size (P=0.035,rs=0.276), invasive depth (P=0.039, rs=0.195), metastasis (P=0.039, rs=0.195), differentiation (P=0.015, rs=0.228) and Laurens classification (P=0.038, rs=0.196), but not with age or gender of patients, growth pattern or TNM staging of gastric cancer (P>0.05). In contrast, Caspase-3 expression showed no correlation with any clinicopathological parameters described above in cancer cells of the primary foci (P>0.05). Interestingly, FasL expression in primary gastric cancer cells paralleled to Caspase-3 expression in infiltrating lymphocytes of the primary foci (P=0.016, chi(2)=5.825). CONCLUSION: Up-regulated expression of FasL and down-regulated expression of Caspase-3 in cancer cells of primary foci play an important role in gastric carcinogenesis. As an effective marker to reveal the biological behaviors, FasL is implicated in differentiation, growth, invasion and metastasis of gastric cancer by inducing apoptosis of infiltrating lymphocytes. Chemical substances derived from the primary foci and metastatic microenvironment can inhibit the growth of metastatic cells by enhancing Caspase-3 expression and diminishing FasL expression.

AIM: To investigate the relation of Fas and Fas ligand (FasL) protein expression with carcinogenesis and metastasis of gastric carcinoma. METHODS: Immunohistochemistry was used to detect Fas and FasL protein expression in 64 gastric carcinoma tissue samples and 20 normal gastric tissue samples. Relation between FasL and Fas expression, age and gender of gastric cancer patients, and pathological subtype and lymph node metastasis of gastric cancer was analyzed. RESULTS: The Fas expression level was significantly higher in normal gastric tissue samples than in gastric carcinoma tissue samples (85.0% vs 25.0%, P < 0.001), while the FasL expression level was significantly lower in normal gastric tissue samples than in gastric carcinoma tissue samples (30.0% vs 81.3%, P < 0.001). The Fas expression level was significantly higher in invasive lymph nodes than in non-invasive lymph nodes (82.9% vs 56.5%, P < 0.003) and in well-differentiated gastric carcinoma tissue samples than in poorly-differentiated gastric carcinoma tissue samples (50.0% vs 18.0%, P = 0.015). The FasL expression level was significantly lower in well-differentiated gastric carcinoma tissue samples than in poorly- differentiated gastric carcinoma tissue samples (42.9% vs 84.0%, P = 0.021). The Fas and FasL expression levels (25.0% and 81.3%) were significantly different in gastric carcinoma tissue samples (P < 0.001), but had a non-linear correlation (P = 0.575). CONCLUSION: Abnormal Fas and FasL expressions in gastric carcinoma and lymph node tissues are involved in carcinogenesis and metastasis of gastric cancer.

BACKGROUND: FAS and its ligand, FASL, have important roles in the neoplasia-immunity relationship. In melanoma, the importance of FAS and FASL remains controversial, despite a group of studies. In this study, we aimed to demonstrate the distribution of FAS/FASL in melanotic lesions and to investigate the correlation between tumor infiltrating lymphocytes and macrophages. METHODS: Ten intra-dermal nevi, 12 primary malignant melanoma, and eight skin and 15 lymph node metastases were included in this study. FAS and FASL were studied in all of the groups using classical labeled streptavidin-biotin immunohistochemical method. tumor infiltrating lymphocyte status and macrophage number demonstrated by CD68 immunostain were also evaluated in primary melanoma and skin metastases. RESULTS: FAS positivity was detected in all of the cases. FASL expressions were seen in 60% of the intra-dermal nevus and in all of the other groups. There were significant differences in FASL between nevus and primary melanoma, nevus and skin metastasis, and nevus and lymph node metastasis. There were strong positive correlations between FAS expression and intra-neoplastic macrophage score and between FASL and density of lymphocyte infiltration in skin metastases. CONCLUSION: Although FAS and FASL expression is a constant feature of melanotic lesions, its diagnostic importance is very limited because of the different results obtained in the past studies. The correlation between FAS status and macrophage number and between FASL status and lymphocyte number in skin metastasis but not in primary lesions might point to diverse FAS/FASL interaction between neoplastic cells and macrophages in the different microenvironments.

OBJECTIVE: In order to characterize the significance of immune system function in patients with advanced renal cell carcinoma (RCC), we investigated the interactive relationships among the following parameters: metastatic characteristics, expression of Fas ligand (FasL) in nephrectomized specimens, immunological parameters, and patient's prognosis. MATERIALS AND METHODS: Thirty-five patients with advanced RCC were stratified into 3 groups according to the characteristics of metastasis timing, at first presentation (mFP), within 5 years of nephrectomy (early-recurrence), after 5 years (late-recurrence). Immunological parameters [hemoglobin, lymphocyte count, neutrophil/lymphocyte ratio (NLR), serum albumin, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and Charlson Comorbidity Index], FasL expression in RCC, and patient prognosis from occurrence of metastasis were compared among the groups. Thirty-five patients were also stratified into 2 groups according to FasL positivity and individual parameters. Patient's prognosis and the remaining immunological parameters were compared between groups. RESULTS: The NLRs of the late-recurrence group were significantly lower than those of the mFP (P = 0.0004) and early-recurrence (P = 0.013) groups. The FasL mRNA positivity of the late-recurrence group was significantly lower than those of the mFP (P = 0.001) and early-recurrence (P = 0.0277) groups. The prognosis of the late-recurrence group was significantly better than that of the early-recurrence group (P = 0.0255). NLRs were significantly lower in the FasL-negative group than in the -positive group (P = 0.0182). The cause-specific survival rates of the ECOG PS 0 group were significantly higher than that of the ECOG PS > 0 group (P < 0.0001). CONCLUSIONS: Our results suggest the associations of the prognosis in advanced RCC with peripheral blood NLR and FasL expression in nephrectomized tumor. The characteristics of lower values of NLR and FasL expression positivity in late-recurrence compared with other metastatic timings suggest strong host immune activity, and may imply relatively long survival. On the other hand, elucidation of the patient's general condition obtained not only by chemical data but also by ECOG PS is crucial in the management of patients with advanced RCC.