Fas相关死亡区蛋白在原发性肝细胞癌中的表达及其与细胞凋亡的关系

Expression of FADD in primary hepatocellular carcinoma and its relationship with hepatic apoptosis

目的研究Ｆａｓ相关死亡区（Ｆａｓ－ａｓｓｏｃｉａｔｅｄ ｄｅａｔｈ ｄｏｍａｉｎ， ＦＡＤＤ）蛋白在原发性肝细胞癌（ｈｅｐａｔｏｃｅｌｌｕｌａｒ ｃａｒｃｉｎｏｍａ，ＨＣＣ）中的表达，并探讨其与ＨＣＣ中细胞凋亡的关系。方法免疫组织化学方法检测ＦＡＤＤ蛋白表达，原位末端标记检测ＨＣＣ细胞凋亡。结果１０例（２５．６％）ＨＣＣ表达ＦＡＤＤ蛋白，与癌旁非癌肝组织相比（５／８，６２．５％），ＨＣＣ中ＦＡＤＤ阳性率显著降低（Ｐ＜０．０５）。１８例分化中等至好的ＨＣＣ中，６例（３３．３％）表达 ＦＡＤＤ，略高于分化差的ＨＣＣ中的阳性率（４／２１， １９０％），但差别没有显著性意义。 Ⅰ／ Ⅱ级 ＨＣＣ中 ８例为ＦＡＤＤ阳性（８／２１，３８．１％），而Ⅲ／Ⅳ级ＨＣＣ中的阳性率仅为１１．１％，差别有显著性意义（Ｐ＜０．０５）。ＦＡＤＤ蛋白表达与患者性别、年龄、肿瘤大小及是否转移无关（Ｐ＞０．０５）。所有标本中均可检测到凋亡的细胞，ＦＡＤＤ蛋白中等至强阳性的ＨＣＣ中，细胞凋亡程度较高，与ＦＡＤＤ表达弱阳性或阴性的ＨＣＣ相比，差别有显著性意义（Ｐ＜０．０５），而癌旁非癌肝组织中，ＦＡＤＤ蛋白表达与细胞凋亡程度无关（Ｐ＞０．０５）。结论ＦＡ?

Objective To investigate the features of Fas-associated death domain(FADD) expression in HCC and to determine its relationship with hepatic apoptosis. Methods Immunohistochemistry method was used to detect FADD expression in HCC. In situ end-labeling(ISEL) was employed to determine apoptotic cells. Results Ten cases(25.6%) of HCC were detected to express FADD protein. The positive rate in HCC was lower than that in non-cancerous adjacent liver tissues which showed as high as 62.5% cases harbored FADD protein(p < 0.05). Six out of 18(33.3%) cases of mid to well differentiated HCC had detectable FADD protein. It is a little higher, but with no statistic significance, than that in poorly differentiated HCC which showed only 19% cases were positive for FADD. In those of grade I / 11. 8 cases (38. l%) were FADD positive, while only 11.1 %(2/18) cases of grade Ⅲ /Ⅳ had FADD protein(P< 0.05). No relationship was found between FADD expression and other clinical features, such as sex, age, tumor size or metastasis. ISEL positive cells could be seen in all cases of HCC. The hepatic apoptosis was associated with FADD expression because more apoptotic cells were detected in those cases which showed moderate to strong FADD positive, as compared with negative or weak FADD positive cases(P< 0.05). While no relationship was found between FADD expression and hepatic apoptosis in non-cancerous adjacent liver tissues. Conclusion Loss of FADD expression plays an important role in HCC carcinogenesis. The apoptosis of cells is associated with FADD expression in HCC.