Abstract 1260: Analysis of death receptor 5 and caspase-8 expression in primary and metastatic head and neck squamous cell carcinoma and their prognostic impact

Abstract

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 approximately 90 primary HNSCC with no evidence of metastasis and approximately 90 primary HNSCC and their matching lymph node metastasis. IHC analysis revealed a significant loss or downregulation of DR5 expression in primary tumors with metastasis [weight index (WI) = 221 ± 64.9 (mean ± SD), n = 92] and their matching lymph node metastasis (WI = 224 ± 71.6, n = 85) compared to primary tumors with no evidence of metastasis (WI = 250 ± 43.9, n = 94) (P < 0.01). A similar trend was also observed in caspase-8 expression although it is not statistically significant. Downregulation of caspase-8 and DR5 expression was significantly correlated with poorly differentiated tumors compared to moderately and well differentiated tumors (P < 0.05). Univariate analysis indicates that, in HNSCC with no metastasis, higher expression of caspase-8 significantly correlated with better disease-free survival and overall survival (P < 0.05 or 0.001) if mean value is used as a cutoff. However, in HNSCC with lymph node metastasis, higher caspase-8 expression significantly correlated with poorer disease-free survival and overall survival (< 0.05 or 0.01). Similar results were also generated when we combined both DR5 and caspase-8. Moreover, multivariable analysis indicates that in patients without lymph node metastasis, high caspase-8 is significantly associated with better survival after adjusting age and stage (P < 0.0001). Together, we suggest that both proteins may be involved in regulation of HNSCC metastasis. (G.C., D.M.S., F.R.K. and S-Y.S. are Georgia Cancer Coalition Distinguished Cancer Scholars. This study was supported by funds from the Georgia Cancer Coalition Distinguished Cancer Scholar and NIH Head and Neck SPORE P50 CA128613 awards) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1260.