A1 Refereed original research article in a scientific journal
Low Expression of Nuclear Toll-like Receptor 4 in Laryngeal Papillomas Transforming into Squamous Cell Carcinoma
Authors: Ilmarinen Taru, Hagström Jaana, Haglund Caj, Auvinen Eeva, Leivo Ilmo, Pitkäranta Anne, Aaltonen Leena-Maija
Publisher: SAGE PUBLICATIONS LTD
Publication year: 2014
Journal: Otolaryngology - Head and Neck Surgery
Journal name in source: OTOLARYNGOLOGY-HEAD AND NECK SURGERY
Journal acronym: OTOLARYNG HEAD NECK
Volume: 151
Issue: 5
First page : 785
Last page: 790
Number of pages: 6
ISSN: 0194-5998
DOI: https://doi.org/10.1177/0194599814549730
Abstract
Objective. The malignant transformation rate of recurrent respiratory papillomatosis (RRP), a disease caused by human papillomavirus (HPV), has varied significantly. Cells of the human immune system express toll-like receptors (TLRs) that recognize particles from viruses and bacteria; TLRs are also present on tumor cells, and down-regulation of TLRs has been shown during the progression of HPV-associated neoplasia. The aim of this study was to determine the malignant transformation rate of laryngeal papillomas (LPs) and analyze the potential of TLR2, TLR4, and TLR9 immunoexpression as indicators of the increased cancer risk.Study Design. Retrospective case-control study.Setting. Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.Subjects and Methods. We reviewed all patients with RRP treated for LPs between 1975 and 2011. Data from the Finnish Cancer Registry confirmed the number of patients diagnosed with laryngeal squamous cell carcinoma (LSCC). Laryngeal tissue specimens from patients developing LSCC were subjected to TLR2, TLR4, and TLR9 immunohistochemistry. Nine patients with RRP without malignant transformation and 19 patients with LSCC without a pre-existing LP served as controls.Results. Nine of 324 patients (2.8%) with RRP developed LSCC. The intensity of nuclear staining of TLR4 was significantly lower in LPs transforming into LSCC than in LPs without malignant transformation. The expression of cytoplasmic TLR4 in LSCC correlated with tumor grade and T stage. Cytoplasmic TLR9 expression was significantly lower in LPs than in LSCC.Conclusion. The expression of TLR4 may serve as a predictive marker of malignant transformation in LPs. High immunoexpression of cytoplasmic TLR4 in LSCC was associated with a more aggressive disease.
Objective. The malignant transformation rate of recurrent respiratory papillomatosis (RRP), a disease caused by human papillomavirus (HPV), has varied significantly. Cells of the human immune system express toll-like receptors (TLRs) that recognize particles from viruses and bacteria; TLRs are also present on tumor cells, and down-regulation of TLRs has been shown during the progression of HPV-associated neoplasia. The aim of this study was to determine the malignant transformation rate of laryngeal papillomas (LPs) and analyze the potential of TLR2, TLR4, and TLR9 immunoexpression as indicators of the increased cancer risk.Study Design. Retrospective case-control study.Setting. Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.Subjects and Methods. We reviewed all patients with RRP treated for LPs between 1975 and 2011. Data from the Finnish Cancer Registry confirmed the number of patients diagnosed with laryngeal squamous cell carcinoma (LSCC). Laryngeal tissue specimens from patients developing LSCC were subjected to TLR2, TLR4, and TLR9 immunohistochemistry. Nine patients with RRP without malignant transformation and 19 patients with LSCC without a pre-existing LP served as controls.Results. Nine of 324 patients (2.8%) with RRP developed LSCC. The intensity of nuclear staining of TLR4 was significantly lower in LPs transforming into LSCC than in LPs without malignant transformation. The expression of cytoplasmic TLR4 in LSCC correlated with tumor grade and T stage. Cytoplasmic TLR9 expression was significantly lower in LPs than in LSCC.Conclusion. The expression of TLR4 may serve as a predictive marker of malignant transformation in LPs. High immunoexpression of cytoplasmic TLR4 in LSCC was associated with a more aggressive disease.
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