Xue Li-yan, Ren Li-qun, Luo Wei, Guan Xiang-jun, Zou Shuang-mei, Zheng Shan, Bi Rui, Xie Yong-qiang, He Zu-gen, Lü Ning
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China.
Zhonghua Yi Xue Za Zhi. 2007 Jan 16;87(3):150-4.
To investigate the expression of five apoptosis-related proteins, Fas, Fas ligand (FasL), Fas-associated death domain protein (FADD), caspase 8, and mutant p53, in human esophageal squamous cell carcinoma (ESCC) tissue, and analyze the association of these proteins with ESCC malignant progression.
116 ESCC specimens obtained during operation. Tissue microarray composed of the 116 specimens of cancerous tissues and corresponding paracancerous normal epithelium tissues was constructed. The expression of Fas, FasL, FADD, caspase 8, and mutant p53 was detected in the ESCC tissues and paracancerous normal epithelium tissues and analysis was conducted for the correlation between the expression of these proteins and the pathoclinical features and prognosis. involvement, differentiated grade, pTNM stages and disease-free survival.
The positive rate of Fas in the ESCC tissues was 41.4%, significantly lower than that in the normal squamous epithelium was 95.7%, P < 0.001). The positive rates of FasL and FADD in the ESCC tissues were 76.7% and 50.0%, both significantly higher than those in the normal squamous epithelium (39.7% and 7.8%, both P < 0.001). Caspase 8 was strongly positive in the whole normal esophageal epithelium tissue except basal and superbasal cells, but negative in ESCC. Mutant p53 protein was negative in the normal esophageal epithelium tissue, with only several cases positive in the basal cells, but was diffusely positive in ESCC tissues with a positive rate of 37.1%. The expression of Fas in the well and moderately differentiated ESCC tissues was significantly higher than in the poorly differentiated ones (P = 0.022). The patients with positive expression of FADD had lower disease-free survival rate (P = 0.0028). The expression of Fas, FasL, caspase 8, and mutant p53 was not related with disease-free survival rate (P > 0.05).
The apoptosis-related markers, such as Fas, FasL, FADD, caspase 8, and mutant p53 protein may play important roles in the development and progression of ESCC, and FADD can be used as a marker to predict the advance and prognosis of ESCC.
探讨凋亡相关蛋白Fas、Fas配体（FasL）、Fas相关死亡结构域蛋白（FADD）、半胱天冬酶8（caspase 8）及突变型p53在人食管鳞状细胞癌（ESCC）组织中的表达情况，并分析这些蛋白与ESCC恶性进展的相关性。
收集手术切除的116例ESCC标本，构建包含116例癌组织及相应癌旁正常上皮组织的组织芯片。检测ESCC组织及癌旁正常上皮组织中Fas、FasL、FADD、caspase 8及突变型p53的表达，并分析这些蛋白表达与临床病理特征及预后（包括浸润情况、分化程度、pTNM分期及无病生存期）的相关性。
ESCC组织中Fas阳性率为41.4%，显著低于正常鳞状上皮的95.7%（P<0.001）。ESCC组织中FasL和FADD的阳性率分别为76.7%和50.0%，均显著高于正常鳞状上皮（分别为39.7%和7.8%，P均<0.001）。Caspase 8在整个正常食管上皮组织中除基底细胞和基底上层细胞外呈强阳性，但在ESCC中呈阴性。突变型p53蛋白在正常食管上皮组织中呈阴性，仅基底细胞中有几例阳性，但在ESCC组织中呈弥漫阳性，阳性率为37.1%。高分化和中分化ESCC组织中Fas的表达显著高于低分化组织（P=0.022）。FADD表达阳性的患者无病生存率较低（P=0.0028）。Fas、FasL、caspase 8及突变型p53的表达与无病生存率无关（P>0.05）。
Fas、FasL、FADD、caspase 8及突变型p53蛋白等凋亡相关标志物可能在ESCC的发生发展中起重要作用，FADD可作为预测ESCC进展及预后的标志物。
