Fas and FasL Expression at Different Stages of Epithelial Malignant Transformation in the Large Intestine and It＇s Significance in Cancerous Apoptotic Evasion

摘要

OBJECTIVE To explore the molecular mechanism of Fas counterattack by observing the expression of Fas and FasL and apoptosis of the epithelium and infiltrative lymphocytes at different stages of intestinal epithelia malignant transformations and further to analyze the relationships among these processes.METHODS Using in-situ hybridization, the expression of Fas mRNA and FasL mRNA in paraffin-embedded tissues was determined. Apoptosis was assessed by the TUNEL method. The tumor specimens were as follows: 37 large intestinal adenocarcinomas, 26 malignant adenomas, 30 tubulo-villous adenomas, and 24 tubular adenomas. Six cases of non-tumor mucosas were used as controls.RESULTS With the progression of malignant transformation, Fas mRNA expression increased slightly in benign adenomas, but significantly decreased in malignant diseases, but, FasL mRNA expression showed an increasing tendency. Apoptotic lymphocyte densities slso showed an increasing tendency. Apoptotic epithelial cell densities increased in benign tumors but decreased in malignant tumors. There was a positive correlation (r=0.672, P<0.001) between FasL expression and apoptotic lymphocyte densities in adenocarcinomas.CONCLUSION With progression of large intestinal epithelial malignant transformation a progressive Fas counterattack develops. Cancer cells express FasL and induce tumor infiltrative lymphocytes to undergo apoptosis allowing the cancer to escape from immune surveillance through Fas-FasL interactions. In addition, the cancer cells may resist death signals transuded by FasL by down regulating Fas expression. This dual process expressed by immune effector cells and cancer cells, forms the Fas resistance mechanism-the prerequisites for Fas counterattack, resulting in inhibition of cancer cell apoptosis. Thus, we suggest that Fas counterattack, together with Fas resistance, both have a relationship to the formation and progression of large intestinal cancer.