title: Nuclear localization of Toll-like receptor 5 in Barrett's esophagus and esophageal adenocarcinoma is associated with metastatic behavior.
abstract: Toll-like receptor 5 (TLR5) recognizes bacterial flagellin. Increased cytoplasmic and nuclear expression of some TLRs has been previously reported in dysplasia in Barrett's esophagus and various malignant lesions in association with survival and metastasis. We assessed nuclear expression of TLR5 in Barrett's esophagus and esophageal adenocarcinoma (n = 94) by immunohistochemistry and immunofluorescent staining. Nuclear expression was observed in the majority of studied lesions with high variation in the proportion of positive nuclei. Expression in lymph node metastases was significantly higher than in esophageal lesions (p < 0.05), except for intestinal metaplasia and low-grade dysplasia. Furthermore, nuclear expression of TLR5 was associated with the presence of lymph node metastases (p = 0.033). In conclusion, we report nuclear TLR5 expression in Barrett's esophagus and adenocarcinoma. Abundance of positive nuclei in association with lymph node metastases suggests that TLR5 is involved in the pathogenesis and dissemination of esophageal adenocarcinoma through as-yet-uncharacterized mechanisms.
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland. olli.helminen@oulu.fi.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland. olli.helminen@oulu.fi.|Department of Anatomy and Cell biology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland. olli.helminen@oulu.fi.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland. olli.helminen@oulu.fi.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland. olli.helminen@oulu.fi.
authors.forename: Olli
authors.identifier: http://orcid.org/0000-0001-9544-6475
authors.initials: O
authors.lastname: Helminen
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Anatomy and Cell biology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Huhta
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Anatomy and Cell biology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Joni
authors.initials: J
authors.lastname: Leppänen
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Anatomy and Cell biology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
authors.affiliation: Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Takala
authors.affiliation: Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Anatomy and Cell biology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Petri P
authors.initials: PP
authors.lastname: Lehenkari
authors.affiliation: Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis / Q000473:pathology*; D001706:Biopsy; D002467:Cell Nucleus / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008679:Metaplasia / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D051198:Toll-Like Receptor 5 / Q000378:metabolism*
chemical_list: C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5
keywords: Barrett’s esophagus; Cell nucleus; Esophageal adenocarcinoma; Toll-like receptor 5