PMID- 20808443
OWN - NLM
STAT- MEDLINE
DCOM- 20101104
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 8
DP  - 2010 Aug 16
TI  - Analysis of death receptor 5 and caspase-8 expression in primary and metastatic 
      head and neck squamous cell carcinoma and their prognostic impact.
PG  - e12178
LID - 10.1371/journal.pone.0012178 [doi]
LID - e12178
AB  - Death receptor 5 (DR5) and caspase-8 are major components in the extrinsic 
      apoptotic pathway. The alterations of the expression of these proteins during the 
      metastasis of head and neck squamous cell carcinoma (HNSCC) and their prognostic 
      impact have not been reported. The present study analyzes the expression of DR5 
      and caspase-8 by immunohistochemistry (IHC) in primary and metastatic HNSCCs and 
      their impact on patient survival. Tumor samples in this study included 100 
      primary HNSCC with no evidence of metastasis, 100 primary HNSCC with lymph node 
      metastasis (LNM) and 100 matching LNM. IHC analysis revealed a significant loss 
      or downregulation of DR5 expression in primary tumors with metastasis and their 
      matching LNM compared to primary tumors with no evidence of metastasis. A similar 
      trend was observed in caspase-8 expression although it was not statistically 
      significant. Downregulation of caspase-8 and DR5 expression was significantly 
      correlated with poorly differentiated tumors compared to moderately and well 
      differentiated tumors. Univariate analysis indicates that, in HNSCC with no 
      metastasis, higher expression of caspase-8 significantly correlated with better 
      disease-free survival and overall survival. However, in HNSCC with LNM, higher 
      caspase-8 expression significantly correlated with poorer disease-free survival 
      and overall survival. Similar results were also generated when we combined both 
      DR5 and caspase-8. Taken together, we suggest that both DR5 and caspase-8 are 
      involved in regulation of HNSCC metastasis. Our findings warrant further 
      investigation on the dual role of caspase-8 in cancer development.
FAU - Elrod, Heath A
AU  - Elrod HA
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, Georgia, United States of 
      America.
FAU - Fan, Songqing
AU  - Fan S
FAU - Muller, Susan
AU  - Muller S
FAU - Chen, Georgia Z
AU  - Chen GZ
FAU - Pan, Lin
AU  - Pan L
FAU - Tighiouart, Mourad
AU  - Tighiouart M
FAU - Shin, Dong M
AU  - Shin DM
FAU - Khuri, Fadlo R
AU  - Khuri FR
FAU - Sun, Shi-Yong
AU  - Sun SY
LA  - eng
GR  - P50 CA128613/CA/NCI NIH HHS/United States
GR  - P50CA128613/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100816
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Carcinoma, Squamous Cell/*diagnosis/genetics/*pathology
MH  - Caspase 8/*metabolism
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Head and Neck Neoplasms/*diagnosis/genetics/*pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*metabolism
MH  - Survival Rate
PMC - PMC2922336
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/09/03 06:00
MHDA- 2010/11/05 06:00
PMCR- 2010/08/16
CRDT- 2010/09/03 06:00
PHST- 2010/05/04 00:00 [received]
PHST- 2010/07/14 00:00 [accepted]
PHST- 2010/09/03 06:00 [entrez]
PHST- 2010/09/03 06:00 [pubmed]
PHST- 2010/11/05 06:00 [medline]
PHST- 2010/08/16 00:00 [pmc-release]
AID - 10-PONE-RA-18543R1 [pii]
AID - 10.1371/journal.pone.0012178 [doi]
PST - epublish
SO  - PLoS One. 2010 Aug 16;5(8):e12178. doi: 10.1371/journal.pone.0012178.