Abstract
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.
Highlights
More than 35,000 people in the United States and more than 500,000 worldwide are estimated to be diagnosed with head and neck squamous cell carcinoma (HNSCC) annually [1,2]
A reduced Death receptor 5 (DR5) expression was reported to be associated with metastatic lesions [35]
The current study revealed a significant downregulation of DR5 expression in primary tumors with lymph node metastasis (LNM) (Tu+met) and their matching LNM compared to primary tumors with no metastasis (Tu2met)
Summary
More than 35,000 people in the United States and more than 500,000 worldwide are estimated to be diagnosed with head and neck squamous cell carcinoma (HNSCC) annually [1,2]. The presence of metastasis in patients with head and neck cancer is common and the 5-year survival rate for patients with lymph node metastasis is approximately 25–50% [3]. Increased DR5 expression was associated with reduced survival in non-small cell lung cancer [7,9]. A recent mouse study has shown that deficiency of TRAIL receptor in mice (only one receptor for TRAIL in mouse) enhances lymph node metastasis (LNM) without affecting primary tumor development [10], suggesting that TRAIL receptor or TRAILTRAIL receptor interaction may be critical for regulation of tumor metastasis. The role of DR5 in metastasis is unknown and the expression of DR5 in primary and metastatic HNSCC has not been examined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
