细胞凋亡调控因子基因在食管上皮癌变过程中的表达及其意义

EXPRESSIONS OF CELL APOPTOSIS REGULATORY FACTOR GENES AND THEIR SIGNIFICANCE IN ESOPHAGEAL CARCINOGENESIS

目的研究细胞凋亡调控因子Fas、Fasl、Fadd和Caspase 8基因在食管上皮癌变过程中的表达及其意义。方法应用免疫组化S-P法检测食管黏膜中Fas、Fasl、Fadd和Caspase 8的蛋白表达。应用碘化丙啶染色和间接免疫荧光标记方法,采用流式细胞仪对食管黏膜组织进行定量检测。结果从食管正常黏膜组织到不典型增生组织和食管癌组织,Fas、Fadd和Caspase 8蛋白表达率呈逐渐下降的趋势,Fasl蛋白表达率呈逐渐上升的趋势,在食管癌和正常组织之间差异有统计学意义,x2分别为5.659,7.73,6.32,5.65,P<0.05或P<0.01。Fas、Fasl和Caspase 8蛋白高中分化鳞癌中蛋白阳性表达率显著高于低分化鳞癌,两者差异有统计学意义,x2分别为4.88,7.79,4.68,P<0.05。与正常黏膜组织和不典型增生组织相比,癌组织中DNA含量明显增高,异倍体细胞显著增加;Fas、Fadd和Caspase 8蛋白表达水平明显降低,t值分别为8.131,7.39,5.44,Fasl基因蛋白表达水平升高,t值为6.671。结论Fas与Fasl的表达失衡与食管癌的发生、发展有密切关系,并与食管癌的分化和免疫逃避有关。Fadd与Caspase 8基因表达异常在食管癌的发生发展中可能起着重要作用。食管上皮癌变过程中,DNA含量及异倍体率增加。

Objective To investigate the effects of the gene expressions of Fas, Fasl , Fadd and caspase 8 in esophageal carcinogenesis Methods Immunohistochemical method was applied to detect the expressions of Fas, Fasl, Fadd and caspase 8 protein in esophageal epithelia. Esophageal epithelia were detected quantitatively by propidium iodide （P I） staining and indirect immunofluorescence of fluorescein isothiocyanate （FITC） using flow cytometry （FCM） . Results The positive rates of Fas , Fadd and caspase 8 protein were decreased, but that of Fasl protein was increased, from normal epithelia to dysplasia and carcinoma tissues gradually. There was a very significant statistical difference between carcinoma and normal epithelia （x^2 = 5.659, 7. 73, 6. 32, 5.65 P 〈 0. 05） . The expressions of Fas, Fasl and caspase 8 were correlated with the degree of tumor differentiation （x^2 = 4. 88, 7.79 4. 68 P 〈 0. 05） . Compared with normal epithelia and dysplasia tissue, the DNA content and heteroploid cells increased significantly in esophageal carcinoma. The expressions of Fas , Fadd and caspase 8 protein decreased obviously while Fasl expression increased in esophageal carcinoma （T = 8. 131, 7.39, 5.44, 6.671 ）. Conclusion The abnormal expressions of Fas and Fasl maybe related with the pathogenesis of esophageal carcinoma and are correlated with degree of differentiation and the immune escape. Fadd and caspase 8 expressions may play an important role in esophageal carsinogenesis. The DNA content and the heteroploid cells are increased significantly in esophageal carcinoma.