Expression Of Fas And Caspase-3 In Renal Cell Carcinoma

Apoptosis mediated by death receptor play an important role in carcinogenesis. Recently, scientist attaches much importance to the apoptosis mediated by Fas receptor via Caspase pathway. Renal cell carcinoma is one of the malignancies in urology. About half of the patients are advanced phase and 20 -30% metastasize at diagnosis. A-bout 40% patients will relapse or metastasize after surgery. Survival rate of 3 and 5 years is low. There is no good therapy except surgery. Fas is a kind of death receptor and participated the apoptosis mediated by Caspase - 3 pathway. It is still unknown about the role of Fas and caspase - 3 in renal cell carcinoma. It is necessary to the study the expression of Fas and Caspase - 3 in renal cell carcinoma.MATERIALS51 cases of renal cell carcinoma samples and 20 cases of pared samples in normal kidney were collected from surgery from 1991 to 2000 year in our hospital. Among of 51 patients, 36 cases were male and 15 cases were female (M: F=2.4:l). The age was between 31 and 78 with an average 6f 55. all patients under went radical nephrec-tomy and renal cell carcinoma was ascertained by postoperativepathol-ogy. (left 34, right, 14, bilateral, 2, multiple, 1) . according to the latest renal cell carcinoma pathological classification: 31 clearrenal cell carcinomas, 11 chromophilie renalcell carcinomas,9 other types(inclu-ding chromophobic renal cell carcinoma, bellini duct type, neuroendo-crine type). According to Fuhrman(1982) renal cell carcinoma morphologic stage system; Gl ?G2 24,G3 - G4 27. according to Roboson stage; I 16, II15,HI -IV 20. 12 cases had lymph node metastasis.METHODSThe samples were fixed with 10% formalin for 48 hours, embedded with paraffin wax, sectioned for 4 jxm, and heat repaired for im-munohistochemistry stain ( SP method). PBS instead of the first antibody was applied as negative control. The work solution of Fas and Caspase -3 was 1 ;50 and 1:150 respectively. 200 cells were counted in HPF. the positive expression was the cell in which brown - yellow particles scattered within cytoplasm or cell membrane. We marked it negative if the positive rate was little than 10% , positive if more than 10%. We applied x test between different groups. Spearman rank test was applied to verify the correlation. All data was dealed with software Spss.RESULTSThe expression site of Fas and Caspase - 3 was almost the same in the normal kidney tissues. The strong st site was proximal tubule and the second strongest one was the collecting duct. Almost no positive cells were found in Henles loop and glomerulus. Fas and Caspase -3 were observed in the cytoplasm or cell membrane in normal kidney and renal cell carcinoma. But Caspase - 3 was weaker than Fas in normal and renal cell carcinoma. Fas and Caspase - 3 coexisted innormal kidney tissue and renal cell carcinoma. Positive rate of Fas and Caspase ?3 in normal kidney were 90. 0% and 80. 0% respectively, but they were 60. 8% and 51.0% for renal cell carcinoma respectively. The expression rate of Fas and Caspase - 3 in renal cell carcinoma was lower than that in normal kidney tissue (P <0. 05). There was positive correlation between Fas and Caspase -3 ( r = 0.516,P <0. 01 ). The positive rate between Gj - G2 and G3 - G4 were 79. 0% and 44. 0% respectively, but they were 71. 0% and 33.0% respectively for Caspase - 3. expression rate of Fas and Caspase - 3 increased when the pathologic stage advanced. In other words, the more malignant the renal cell carcinoma, the lower the positive expression rate. There was no statistical difference between pathologic type, UICC stage and lymph node metastasis.DISCUSSIONWith the advancement in biology, scientist has realized that the apoptosis play an important role in the tumor therapy. Up to now, there are many death receptors that contribute to cell apoptosis. These death receptors are Fas, TNFR1, DR3 and DR4. Fas protein, Fas gene product, is a kind of transmembrane protein, a member of nerve growth factor and tumor necrosis factor superfamily.