title: Biomarkers of apoptosis and survival in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Cancer of the esophagus is a deadly malignancy, and development of biomarkers that predict survival is an urgent need. The apoptotic pathways have been hypothesized as important in progression of esophageal squamous cell carcinoma (ESCC). We investigated a panel of proteins that regulate apoptosis as candidate of biomarkers of prognosis in ESCC.
  
  
  METHODS
  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.
  
  
  RESULTS
  Five markers showed strong inter-marker correlations (r > or = 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.
  
  
  CONCLUSIONS
  Individual biomarkers in the apoptosis pathway do not appear to predict survival of patients with ESCC.
authors.affiliation: Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. takikitm@mail.nih.gov
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takikita
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Shou
authors.forename: Quan-Hong
authors.initials: QH
authors.lastname: Wang
authors.forename: Carol
authors.initials: C
authors.lastname: Giffen
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D013534:Survival; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor