Biomarkers of apoptosis and survival in esophageal squamous cell carcinoma.
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.
Takikita
Mikiko
M
Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. takikitm@mail.nih.gov
Hu
Nan
N
Shou
Jian-Zhong
JZ
Wang
Quan-Hong
QH
Giffen
Carol
C
Taylor
Philip R
PR
Hewitt
Stephen M
SM
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
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor