Argyrios G Daskalopoulos1, Dimitrios Avgoustidis2, Risa Chaisuparat3, Maria Karanikou4, Andreas C Lazaris4, Alexandra Sklavounou5, Nikolaos G Nikitakis5. 1. Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece. Electronic address: Adaskal@hotmail.gr. 2. Department of Oral and Maxillofacial Surgery, "Evaggelismos" General Hospital, National and Kapodistrian University of Athens, Greece. 3. Department of Oral Pathology, Faculty of Dentistry, Chulalongkom University, Bangkok, Thailand. 4. Department of Pathology, Medical School, National and Kapodistrian University of Athens, Greece. 5. Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece.
Abstract
OBJECTIVES: Toll-like receptors (TLRs) may promote or inhibit tumor progression. The aim of this study was to assess the expression of TLR4 and TLR9 and their downstream targets in oral tongue squamous cell carcinoma (OTSCC) in correlation with histopathologic parameters and human papillomavirus (HPV) status. STUDY DESIGN: OTSCC (fully or superficially invasive and in situ) were studied. Immunohistochemical expression of TLR4, TLR9, nuclear factor-κΒ (NF-κΒ/p65), and interferon-β (IFN-β) was evaluated in tumor and inflammatory cells and in adjacent morphologically normal mucosa. HPV status was also determined. RESULTS: TLR4 showed increased expression levels in tumor and infiltrating inflammatory cells compared with adjacent mucosa, especially in fully invasive cases; a negative correlation between TLR4 levels in inflammatory cells and tumor grade was observed. TLR9 was upregulated in tumor and infiltrating inflammatory cells compared with the adjacent mucosa; its expression in inflammatory cells was higher in well differentiated tumors. NF-κΒ and IFN-β were elevated in cancerous tissues, especially in fully invasive cases, and positively correlated with TLR4 and/or TLR9. HPV positivity (detected in 15.9% of the cases) demonstrated positive correlation with TLR9 and NF-κΒ levels. CONCLUSIONS: TLR4 and TLR9 are upregulated in OTSCC and its microenvironment and, by affecting important downstream molecules, such as NF-κB and IFN-β, may play a role in oral cancer development and progression.
OBJECTIVES: Toll-like receptors (TLRs) may promote or inhibit tumor progression. The aim of this study was to assess the expression of TLR4 and TLR9 and their downstream targets in oral tongue squamous cell carcinoma (OTSCC) in correlation with histopathologic parameters and human papillomavirus (HPV) status. STUDY DESIGN: OTSCC (fully or superficially invasive and in situ) were studied. Immunohistochemical expression of TLR4, TLR9, nuclear factor-κΒ (NF-κΒ/p65), and interferon-β (IFN-β) was evaluated in tumor and inflammatory cells and in adjacent morphologically normal mucosa. HPV status was also determined. RESULTS: TLR4 showed increased expression levels in tumor and infiltrating inflammatory cells compared with adjacent mucosa, especially in fully invasive cases; a negative correlation between TLR4 levels in inflammatory cells and tumor grade was observed. TLR9 was upregulated in tumor and infiltrating inflammatory cells compared with the adjacent mucosa; its expression in inflammatory cells was higher in well differentiated tumors. NF-κΒ and IFN-β were elevated in cancerous tissues, especially in fully invasive cases, and positively correlated with TLR4 and/or TLR9. HPV positivity (detected in 15.9% of the cases) demonstrated positive correlation with TLR9 and NF-κΒ levels. CONCLUSIONS: TLR4 and TLR9 are upregulated in OTSCC and its microenvironment and, by affecting important downstream molecules, such as NF-κB and IFN-β, may play a role in oral cancer development and progression.
Authors: Fernanda Visioli; Julia Silveira Nunes; Maria Carmela Pedicillo; Rosalia Leonardi; Angela Santoro; Gian Franco Zannoni; Gabriella Aquino; Margherita Cerrone; Monica Cantile; Nunzia Simona Losito; Vito Rodolico; Giuseppina Campisi; Giuseppe Colella; Ilenia Sara De Stefano; Maria Antonietta Ramunno; Cristina Pizzulli; Marco Visconti; Lorenzo Lo Muzio; Giuseppe Pannone Journal: Biomolecules Date: 2022-02-28