Analysis of death receptor 5 and caspase-8 expression in primary and metastatic head and neck squamous cell carcinoma and their prognostic impact.
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.
Elrod
Heath A
HA
Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia, United States of America.
Fan
Songqing
S
Muller
Susan
S
Chen
Georgia Z
GZ
Pan
Lin
L
Tighiouart
Mourad
M
Shin
Dong M
DM
Khuri
Fadlo R
FR
Sun
Shi-Yong
SY
D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D053181:Caspase 8 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D015996:Survival Rate
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053181:Caspase 8
J Biol Chem. 2006 Feb 17;281(7):4457-66
16361262
Cancer Res. 2009 May 1;69(9):3755-63
19383910
Apoptosis. 2002 Oct;7(5):449-59
12207178
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
19474385
Br J Cancer. 1999 Oct;81(4):592-9
10574243
Gynecol Oncol. 2010 Mar;116(3):549-55
19959214
Cancer Biol Ther. 2002 Jan-Feb;1(1):65-9
12170765
J Clin Oncol. 2006 Nov 1;24(31):4998-5004
17075118
Oncology. 2008;74(3-4):229-36
18716417
Nat Med. 2000 May;6(5):529-35
10802708
Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):203-11
19695437
Cancer Res. 2006 Oct 15;66(20):10016-23
17047064
J Immunol. 2007 Jan 15;178(2):936-43
17202355
J Biol Chem. 2004 Dec 17;279(51):53683-90
15471877
Oncogene. 2005 Jan 6;24(1):141-7
15531912
Cancer Res. 2007 Dec 15;67(24):11505-9
18089778
Cytokine Growth Factor Rev. 2008 Jun-Aug;19(3-4):325-31
18495520
Hum Pathol. 2006 Oct;37(10):1286-94
16949935
Cancer Res. 2006 Apr 15;66(8):4273-8
16618751
Cancer. 2008 Jul 1;113(1):97-107
18473353
Clin Cancer Res. 2003 Dec 15;9(17):6401-9
14695141
Cancer Res. 2008 Jun 15;68(12):4491-3
18559490
Clin Cancer Res. 2010 Mar 15;16(6):1701-8
20197482
Clin Cancer Res. 2003 Aug 15;9(9):3397-405
12960128
Gynecol Oncol. 2005 Mar;96(3):705-13
15721415
Toxicol Lett. 2007 Apr 25;170(2):134-45
17399918
Cancer Treat Res. 2006;130:141-65
16610707
J Mol Med (Berl). 2009 Oct;87(10):995-1007
19680616
Nature. 2000 Oct 12;407(6805):770-6
11048727
Cancer Res. 2007 Dec 15;67(24):11704-11
18089800
Rev Recent Clin Trials. 2009 Jan;4(1):34-41
19149761
Eur J Cancer. 2005 May;41(8):1195-202
15911244
Histopathology. 1998 Nov;33(5):432-9
9839167
Eur J Cancer. 2002 Jan;38(1):83-91
11750844
Cell Oncol. 2007;29(5):409-19
17726263
Chest. 2004 Apr;125(4):1467-71
15078760
Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):337-48
12787570
Cancer Res. 2007 May 15;67(10):4774-82
17510406
Cell Death Differ. 2003 Mar;10(3):356-64
12700635
APMIS. 2002 Nov;110(11):825-32
12588423
Clin Cancer Res. 2004 Dec 15;10(24):8451-9
15625067
Br J Cancer. 2005 Apr 25;92(8):1341-8
15846296
CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
15761078
Nature. 2006 Jan 5;439(7072):95-9
16397500
Cancer Res. 2008 Feb 1;68(3):909-17
18245494
Cancer. 2008 Jul 1;113(1):135-42
18457325
Cancer Res. 2005 Feb 1;65(3):815-21
15705878
Cancer Res. 2002 Oct 15;62(20):5897-901
12384554
J Clin Invest. 2008 Jan;118(1):100-10
18079967
Oncogene. 2006 Nov 30;25(56):7434-9
16751802
Nat Med. 2001 Jan;7(1):94-100
11135622
J Biol Chem. 2008 May 9;283(19):13031-4
18216014