Youssef, H., Omar, T., Fouad, H., El-Sheikh, S., El Achy, S., Afifi, M. (2018). EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study). Alexandria Dental Journal, 43(3), 65-69. doi: 10.21608/adjalexu.2018.57996
Hayat A. Youssef; Taissir A. Omar; Hamed A. Fouad; Sahar M. El-Sheikh; Samar El Achy; Marwa M. Afifi. "EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study)". Alexandria Dental Journal, 43, 3, 2018, 65-69. doi: 10.21608/adjalexu.2018.57996
Youssef, H., Omar, T., Fouad, H., El-Sheikh, S., El Achy, S., Afifi, M. (2018). 'EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study)', Alexandria Dental Journal, 43(3), pp. 65-69. doi: 10.21608/adjalexu.2018.57996
Youssef, H., Omar, T., Fouad, H., El-Sheikh, S., El Achy, S., Afifi, M. EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study). Alexandria Dental Journal, 2018; 43(3): 65-69. doi: 10.21608/adjalexu.2018.57996
EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study)
1Assistant lecturer in Oral Pathology Department, Faculty of Dentistry, Alexandria University
2Professor in Oral Pathology Department, Faculty of Dentistry, Alexandria University.
3Professor in Oral Pathology Department, Faculty of Dentistry, Alexandria University
4Lecturer in Pathology Department, Faculty of Medicine, Alexandria University
5Lecturer in Oral Pathology Department, Faculty of Dentistry, Alexandria University
Abstract
INTRODUCTION: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers with high mortality and morbidity rates. Lymph node (LN) metastasis is one of the most important factors in the treatment and prognosis of patients with OSCC. It reduces the overall survival by nearly half. Toll like receptors (TLRs) are evolutionarily conserved proteins and major type of receptors involved in both innate and adaptive immunities and defense against pathogens. TLR4 was the first member of the TLR family to be discovered. It was verified that TLR4 is expressed in many types of tumors including OSCC. The correlation between the expression of this receptor and the presence of nodal metastasis has been studied. Involvement of TLR4 in the invasion and metastasis potentials may thus suggest the use of this protein as a prognostic marker for OSCC and may provide a new insight in the treatment strategy. OBJECTIVES: The aim of the present study was to assess the expression of TLR4 in the primary tumor of OSCC and correlate it with the lymph node status. MATERIALS AND METHODS: TLR4 expression was calculated in 30 OSCC cases. The specimens were taken from the primary tumor of 15 cases proved to have positive lymph nodes and another 15 cases with negative lymph nodes. Immunohistochemical (IHC) staining was performed using the Labeled Strept-Avidin Biotin complex method (LSAB), using the anti-TLR4 antibody. RESULTS: TLR4 was expressed in the OSCC cases and was significantly higher in cases with positive lymph node metastasis than those without. CONCLUSIONS: TLR4 expression could be used as a prognostic marker for OSCC as an indicator for metastasis.
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4-5):309-16.
Scully C, Bagan J. Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis. 2009 Sep;15(6):388-99.
Feller L, Lemmer J. Oral Squamous Cell Carcinoma: Epidemiology, Clinical Presentation and Treatment2012.
Omar K, Camile SF, Newell WJ. Oral and oropharyngeal cancer in the Middle East and North Africa: Incidence, mortality, trends, and gaps in public databases as presented to the Global Oral Cancer Forum. Translational Research in Oral Oncology. 2017 2017/01/01;2:2057178X17698480.
de Vicente JC, Lequerica-Fernandez P, Santamaria J, Fresno MF. Expression of MMP-7 and MT1-MMP in oral squamous cell carcinoma as predictive indicator for tumor invasion and prognosis. J Oral Pathol Med. 2007 Aug;36(7):415-24.
Lodder WL, Pameijer FA, Rasch CR, van den Brekel MW, Balm AJ. Prognostic significance of radiologically determined neck node volume in head and neck cancer: a systematic review. Oral Oncol. 2012 Apr;48(4):298-302.
Luongo de Matos L, Manfro G, Vieira dos Santos R, Stabenow E, Sobroza de Mello E, Alves VAF, et al. Tumor Thickness As A Predictive Factor Of Lymph Node Metastasis And Disease Recurrence In T1n0 And T2n0 Squamous Cell Carcinoma Of The Oral Tongue. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology. 2014.
Layland MK, Sessions DG, Lenox J. The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+. Laryngoscope. 2005;115(4):629-39.
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006 Feb 24;124(4):783-801.
Anderson KV, Bokla L, Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell. 1985 Oct;42(3):791-8.
Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996 Sep 20;86(6):973-83.
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010 May;11(5):373-84.
Ioannou S, Voulgarelis M. Toll-like receptors, tissue injury, and tumourigenesis. Mediators Inflamm. 2010.
Medzhitov R, Preston-Hurlburt P, Janeway CA, Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997 Jul 24;388(6640):394-7.
Gong W, Wang ZY, Chen GX, Liu YQ, Gu XY, Liu WW. Invasion potential of H22 hepatocarcinoma cells is increased by HMGB1-induced tumor NF-kappaB signaling via initiation of HSP70. Oncol Rep. 2013 Sep;30(3):1249-56.
Thuringer D, Hammann A, Benikhlef N, Fourmaux E, Bouchot A, Wettstein G, et al. Transactivation of the epidermal growth factor receptor by heat shock protein 90 via Toll-like receptor 4 contributes to the migration of glioblastoma cells. J Biol Chem. 2011 Feb 4;286(5):3418- 28.
Wang C, Fei G, Liu Z, Li Q, Xu Z, Ren T. HMGB1 was a pivotal synergistic effecor for CpG oligonucleotide to enhance the progression of human lung cancer cells. Cancer Biol Ther. 2012 Jul;13(9):727-36.
Yang H, Wang B, Wang T, Xu L, He C, Wen H, et al. Tolllike receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis. PLoS One. 2014;9(10):e109980.
Block MS, Vierkant RA, Rambau PF, Winham SJ, Wagner P, Traficante N, et al. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer. Mayo Clinic Proceedings. 2018 2018/03/01/;93(3):307-20.
Huang HY, Zhang ZJ, Cao CB, Wang N, Liu FF, Peng JQ, et al. The TLR4/NF-kappaB signaling pathway mediates the growth of colon cancer. Eur Rev Med Pharmacol Sci. 2014;18(24):3834-43.
Takazawa Y, Kiniwa Y, Ogawa E, Uchiyama A, Ashida A, Uhara H, et al. Toll-like receptor 4 signaling promotes the migration of human melanoma cells. Tohoku J Exp Med. 2014 Sep;234(1):57-65.
Makinen LK, Atula T, Hayry V, Jouhi L, Datta N, Lehtonen S, et al. Predictive role of Toll-like receptors 2, 4, and 9 in oral tongue squamous cell carcinoma. Oral Oncol. 2015 Jan;51(1):96-102.
Szczepanski MJ, Czystowska M, Szajnik M, Harasymczuk M, Boyiadzis M, Kruk-Zagajewska A, et al. Triggering of Toll-like Receptor 4 Expressed on Human Head and Neck Squamous Cell Carcinoma Promotes Tumor Development and Protects the Tumor from Immune Attack. Cancer Research. 2009;69(7):3105-13.
Rich AM, Hussaini HM, Parachuru VP, Seymour GJ. Tolllike receptors and cancer, particularly oral squamous cell carcinoma. Front Immunol. 2014;5:464.
Sun Z, Luo Q, Ye D, Chen W, Chen F. Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis. Molecular Cancer. [journal article]. 2012 May 14;11(1):33.
Masood R, Hochstim C, Cervenka B, Zu S, Baniwal SK, Patel V, et al. A novel orthotopic mouse model of head and neck cancer and lymph node metastasis. Oncogenesis. [Original Article]. 2013;2:e68.
Syrbu SI, Cohen MB. An enhanced antigen-retrieval protocol for immunohistochemical staining of formalinfixed, paraffin-embedded tissues. Methods Mol Biol. 2011;717:101-10.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108.
Yang J, Liu D, Khatri KS, Wang J, Zhang G, Meng C, et al. Prognostic value of toll-like receptor 4 and nuclear factor-kappaBp65 in oral squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016 Dec;122(6):753-64 e1.
Wang H, Rayburn ER, Wang W, Kandimalla ER, Agrawal S, Zhang R. Chemotherapy and chemosensitization of nonsmall cell lung cancer with a novel immunomodulatory oligonucleotide targeting Toll-like receptor 9. Mol Cancer Ther. 2006 Jun;5(6):1585-92.
Ren WH, Zhang LM, Liu HQ, Gao L, Chen C, Qiang C, et al. Protein overexpression of CIRP and TLR4 in oral squamous cell carcinoma: an immunohistochemical and clinical correlation analysis. Med Oncol. 2014 Aug;31(8):120.
Dang S, Peng Y, Ye L, Wang Y, Qian Z, Chen Y, et al. Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7. Clin Dev Immunol. 2013;2013:712561.
Zhang H, Zhang S. The expression of Foxp3 and TLR4 in cervical cancer: association with immune escape and clinical pathology. Arch Gynecol Obstet. 2017 Mar;295(3):705-12.
Chen G, Xu M, Chen J, Hong L, Lin W, Zhao S, et al. Clinicopathological Features and Increased Expression of Toll-Like Receptor 4 of Gastric Cardia Cancer in a HighRisk Chinese Population. Journal of Immunology Research. 2018;2018:10.
Li D, Jin Y, Sun Y, Lei J, Liu C. Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo. Int J Oncol. 2014 Aug;45(2):813-21.
Simiantonaki N, Kurzik-Dumke U, Karyofylli G, Jayasinghe C, Michel-Schmidt R, Kirkpatrick CJ. Reduced expression of TLR4 is associated with the metastatic status of human colorectal cancer. Int J Mol Med. 2007 Jul;20(1):21-9.
Davis MB, Vasquez-Dunddel D, Fu J, Albesiano E, Pardoll D, Kim YJ. Intratumoral administration of TLR4 agonist absorbed into a cellular vector improves antitumor responses. Clin Cancer Res. 2011 Jun 15;17(12):3984-92.
Lamrani M, Sassi N, Paul C, Yousfi N, Boucher JL, Gauthier N, et al. TLR4/IFNgamma pathways induce tumor regression via NOS II-dependent NO and ROS production in murine breast cancer models. Oncoimmunology. 2016 May;5(5):e1123369.