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

作者：Huhta Heikki; Helminen Olli; Lehenkari Petri P; Saarnio Juha; Karttunen Tuomo J; Kauppila Joonas H^*

来源：Oncotarget, 2016, 7(17): 23658-23667.

DOI：10.18632/oncotarget.8151

• toll-like receptor 1
• toll-like receptor 2
• toll-like receptor 4
• toll-like receptor 6
• esophageal adenocarcinoma

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.

• 出版日期2016-4-26