TLR4 Expression in Ex-Lichenoid Lesions—Oral Squamous Cell Carcinomas and Its Surrounding Epithelium: The Role of Tumor Inflammatory Microenvironment
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
Affiliations
Fernanda Visioli
Department of Oral Pathology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035003, RS, Brazil
Julia Silveira Nunes
Department of Oral Pathology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035003, RS, Brazil
Maria Carmela Pedicillo
Pathological Anatomy Unit, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Rosalia Leonardi
Department of Medical-Surgical Specialties, University of Catania, 95124 Catania, Italy
Angela Santoro
Department of Sciences of the Women and Child Health, Fondazione Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Gian Franco Zannoni
Department of Sciences of the Women and Child Health, Fondazione Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Gabriella Aquino
Pathology Unit, National Cancer Institute, Fondazione “G. Pascale”, Via Mariano Semmola, 80131 Napoli, Italy
Margherita Cerrone
Pathology Unit, National Cancer Institute, Fondazione “G. Pascale”, Via Mariano Semmola, 80131 Napoli, Italy
Monica Cantile
Pathology Unit, National Cancer Institute, Fondazione “G. Pascale”, Via Mariano Semmola, 80131 Napoli, Italy
Nunzia Simona Losito
Pathology Unit, National Cancer Institute, Fondazione “G. Pascale”, Via Mariano Semmola, 80131 Napoli, Italy
Vito Rodolico
Department of Sciences for the Promotion of the Maternal and Childhood Health “G. D’Alessandro”, Section of Anatomic Pathology, University of Palermo, A.O.U. Policlinico “P. Giaccone”, 90133 Palermo, Italy
Giuseppina Campisi
Department of Surgical, Oncological and Oral Sciences, University of Palermo, Via del Vespro 129, 90133 Palermo, Italy
Giuseppe Colella
Department of Head and Neck Surgery, Second University of Naples, 80131 Naples, Italy
Ilenia Sara De Stefano
Pathological Anatomy Unit, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Maria Antonietta Ramunno
Pathological Anatomy Unit, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Cristina Pizzulli
Pathological Anatomy Unit, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Marco Visconti
Pathological Anatomy Unit, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Lorenzo Lo Muzio
Department of Clinical and Experimental Medicine, Oral Pathology Unit, University of Foggia, 71122 Foggia, Italy
Giuseppe Pannone
Pathological Anatomy Unit, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immunohistochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex–OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development.
