BACKGROUND: Stimulation of Toll-like receptor 9 (TLR9) has been linked to invasion in various cancer cells in vitro. We investigated TLR9 expression in normal, dysplastic and malignant esophageal squamous epithelium. METHODS: TLR9 expression was analyzed by immunohistochemistry in 46 cases of esophageal squamous cell carcinoma, including 12 cases with adjacent squamous dysplasia and 24 cases with normal esophageal epithelium. TLR9 expression was compared with tumor grade, stage, proliferation, apoptosis and vascular density. RESULTS: In normal esophageal squamous epithelium, TLR9 staining intensity decreased linearly from the basal layers to the superficial layers (p < 0.001). Strong TLR9 expression was detected across full thickness of high-grade dysplasia, the intensity clearly differing from the normal squamous epithelium and squamous cell carcinoma (p < 0.001). All squamous cell carcinomas exhibited TLR9 expression that was positively associated with a high grade (p < 0.05), the presence of lymph node metastases (p < 0.05) and previously undetected distant metastases (p < 0.05). CONCLUSIONS: Expression of TLR9 in the basal parts of normal esophageal epithelium suggests a role related to cell proliferation and differentation. TLR9 upregulation detected in dysplastic epithelium and in disseminated carcinomas indicates that this protein may serve as a novel marker for esophageal squamous dysplasia and carcinoma with metastatic potential.
BACKGROUND: Stimulation of Toll-like receptor 9 (TLR9) has been linked to invasion in various cancer cells in vitro. We investigated TLR9 expression in normal, dysplastic and malignant esophageal squamous epithelium. METHODS:TLR9 expression was analyzed by immunohistochemistry in 46 cases of esophageal squamous cell carcinoma, including 12 cases with adjacent squamous dysplasia and 24 cases with normal esophageal epithelium. TLR9 expression was compared with tumor grade, stage, proliferation, apoptosis and vascular density. RESULTS: In normal esophageal squamous epithelium, TLR9 staining intensity decreased linearly from the basal layers to the superficial layers (p < 0.001). Strong TLR9 expression was detected across full thickness of high-grade dysplasia, the intensity clearly differing from the normal squamous epithelium and squamous cell carcinoma (p < 0.001). All squamous cell carcinomas exhibited TLR9 expression that was positively associated with a high grade (p < 0.05), the presence of lymph node metastases (p < 0.05) and previously undetected distant metastases (p < 0.05). CONCLUSIONS: Expression of TLR9 in the basal parts of normal esophageal epithelium suggests a role related to cell proliferation and differentation. TLR9 upregulation detected in dysplastic epithelium and in disseminated carcinomas indicates that this protein may serve as a novel marker for esophageal squamous dysplasia and carcinoma with metastatic potential.
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Authors: Mikko Mella; Joonas H Kauppila; Peeter Karihtala; Petri Lehenkari; Arja Jukkola-Vuorinen; Ylermi Soini; Päivi Auvinen; Markku H Vaarala; Hanna Ronkainen; Saila Kauppila; Kirsi-Maria Haapasaari; Katri S Vuopala; Katri S Selander Journal: Oncoimmunology Date: 2015-05-22 Impact factor: 8.110
Authors: Olli Helminen; Heikki Huhta; Petri P Lehenkari; Juha Saarnio; Tuomo J Karttunen; Joonas H Kauppila Journal: Oncoimmunology Date: 2016-01-25 Impact factor: 8.110
Authors: Olli Helminen; Heikki Huhta; Heikki Takala; Petri P Lehenkari; Juha Saarnio; Joonas H Kauppila; Tuomo J Karttunen Journal: Virchows Arch Date: 2013-11-13 Impact factor: 4.064
Authors: George Couch; James E Redman; Lorenz Wernisch; Richard Newton; Shalini Malhotra; Sanford M Dawsey; Pierre Lao-Sirieix; Rebecca C Fitzgerald Journal: Cancer Prev Res (Phila) Date: 2016-04-12
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