Research Papers:

Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett’s esophagus, dysplasia and adenocarcinoma

Heikki Huhta, Olli Helminen, Petri P. Lehenkari, Juha Saarnio, Tuomo J. Karttunen and Joonas H. Kauppila _

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Oncotarget. 2016; 7:23658-23667. https://doi.org/10.18632/oncotarget.8151

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Heikki Huhta1,2,4,5,*, Olli Helminen1,2,4,5,*, Petri P. Lehenkari2,3,4,5, Juha Saarnio2,4,5, Tuomo J. Karttunen1,4,5, Joonas H. Kauppila1,2,4,5

1Department of Pathology, University of Oulu, 90014 Oulu, Finland

2Department of Surgery, University of Oulu, 90014 Oulu, Finland

3Department of Anatomy and Cell biology, University of Oulu, 90014 Oulu, Finland

4Medical Research Center Oulu, 90014 Oulu, Finland

5Oulu University Hospital, 90029 Oulu, Finland

*These authors are contributed equally to this work

Correspondence to:

Joonas H. Kauppila, e-mail: joonas.kauppila@oulu.fi

Keywords: Toll-like receptor 1, Toll-like receptor 2, Toll-like receptor 4, Toll-like receptor 6, esophageal adenocarcinoma

Received: December 17, 2015     Accepted: March 02, 2016     Published: March 17, 2016


Background: Toll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett’s esophagus, dysplasia and esophageal adenocarcinoma.

Methods: TLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99).

Results: We found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett’s mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis.

Conclusions: TLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma.

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