PMID- 25205638 OWN - NLM STAT- MEDLINE DCOM- 20160429 LR - 20220408 IS - 1097-6817 (Electronic) IS - 0194-5998 (Linking) VI - 151 IP - 5 DP - 2014 Nov TI - Low expression of nuclear Toll-like receptor 4 in laryngeal papillomas transforming into squamous cell carcinoma. PG - 785-90 LID - 10.1177/0194599814549730 [doi] AB - 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. CI - (c) American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014. FAU - Ilmarinen, Taru AU - Ilmarinen T AD - Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland taru.ilmarinen@helsinki.fi. FAU - Hagstrom, Jaana AU - Hagstrom J AD - Department of Pathology, Haartman Institute, Helsinki University Hospital, University of Helsinki, Helsinki, Finland Helsinki University Hospital Laboratory, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. FAU - Haglund, Caj AU - Haglund C AD - Department of Pathology, Haartman Institute, Helsinki University Hospital, University of Helsinki, Helsinki, Finland Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. FAU - Auvinen, Eeva AU - Auvinen E AD - Helsinki University Hospital Laboratory, Helsinki University Hospital, University of Helsinki, Helsinki, Finland Department of Virology, Haartman Institute, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. FAU - Leivo, Ilmo AU - Leivo I AD - Department of Pathology, Turku University Hospital, University of Turku, Turku, Finland. FAU - Pitkaranta, Anne AU - Pitkaranta A AD - Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. FAU - Aaltonen, Leena-Maija AU - Aaltonen LM AD - Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140909 PL - England TA - Otolaryngol Head Neck Surg JT - Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery JID - 8508176 RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - Laryngeal papillomatosis SB - IM MH - Adult MH - Aged MH - Carcinoma, Squamous Cell/*pathology MH - Case-Control Studies MH - Cell Nucleus MH - *Cell Transformation, Neoplastic MH - Female MH - Head and Neck Neoplasms/*pathology MH - Humans MH - Laryngeal Neoplasms/metabolism/*pathology MH - Male MH - Middle Aged MH - Papilloma/*metabolism/*pathology MH - Retrospective Studies MH - Squamous Cell Carcinoma of Head and Neck MH - Toll-Like Receptor 4/*biosynthesis OTO - NOTNLM OT - human papillomavirus OT - laryngeal papilloma OT - malignant transformation OT - recurrent respiratory papillomatosis OT - squamous cell carcinoma OT - toll-like receptor EDAT- 2014/09/11 06:00 MHDA- 2016/04/30 06:00 CRDT- 2014/09/11 06:00 PHST- 2014/09/11 06:00 [entrez] PHST- 2014/09/11 06:00 [pubmed] PHST- 2016/04/30 06:00 [medline] AID - 0194599814549730 [pii] AID - 10.1177/0194599814549730 [doi] PST - ppublish SO - Otolaryngol Head Neck Surg. 2014 Nov;151(5):785-90. doi: 10.1177/0194599814549730. Epub 2014 Sep 9.