%0 Journal Article
%T Biomarkers of apoptosis and survival in esophageal squamous cell carcinoma
%A Mikiko Takikita
%A Nan Hu
%A Jian-zhong Shou
%A Quan-Hong Wang
%A Carol Giffen
%A Philip R Taylor
%A Stephen M Hewitt
%J BMC Cancer
%D 2009
%I BioMed Central
%R 10.1186/1471-2407-9-310
%X Tissue microarray (TMA) including 313 surgically-resected cases of ESCC specimens was built for immunohistochemical interrogation. We evaluated seven genes in the FasL-Fas apoptotic pathway - FasL, Fas, FAS-associated death domain protein (FADD), phosphorylated-FADD, and caspase 8 and 10, and the antiapoptotic protein bcl-2. We studied pathway integrity and relations to risk and clinical factors, and determined the prognostic significance of each marker.Five markers showed strong inter-marker correlations (r ¡Ý 0.28, p < 0.001), including FasL, Fas, FADD, and caspases 8 and 10. FasL and FADD also showed modest correlations with one or more cancer risk factors, but none of the markers was significantly associated with either tumor stage or lymph node metastasis, the only two clinical factors that predicted survival in these ESCC cases. Multivariate-adjusted proportional hazard regression models showed no association between protein expression and risk of death for any of the seven markers examined.Individual biomarkers in the apoptosis pathway do not appear to predict survival of patients with ESCC.Fas-mediated apoptosis is thought to be involved in the initiation and development of esophageal squamous cell carcinoma (ESCC). Previous gene expression profiling of ESCC showed over-expression of FAS-associated death domain RNA (FADD) and under-expression of Fas and caspase 8 [1]. The phosphorylated form of FADD (p-FADD) has recently been reported to regulate apoptotic activity [2]. Although the role of p-FADD in ESCC outcome is unclear, higher levels of p-FADD protein correlated with reduced survival in patients with lung adenocarcinomas [3] and prostate cancer [4].Using an ESCC tissue microarray (TMA) [5], we explored the expression of FasL, Fas, FADD, p-FADD, caspase 8 and 10, which are proteins involved in the FasL-Fas apoptotic pathway, and the antiapoptotic protein bcl-2. We determined the prevalence of protein expression for each marker, investigated pathway integr
%U http://www.biomedcentral.com/1471-2407/9/310