Huhta Heikki, Helminen Olli, Lehenkari Petri P, Saarnio Juha, Karttunen Tuomo J, Kauppila Joonas H
Department of Pathology, University of Oulu, 90014 Oulu, Finland.
Department of Surgery, University of Oulu, 90014 Oulu, Finland.
Oncotarget. 2016 Apr 26;7(17):23658-67. doi: 10.18632/oncotarget.8151.
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.
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).
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.
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.
Toll样受体（TLRs）可识别微生物和内源性配体，且已证实在食管癌中发挥作用。在本研究中，我们特别评估了在巴雷特食管、发育异常和食管腺癌中感知细菌细胞壁成分的TLRs。
对TLR1、TLR2、TLR4和TLR6进行免疫组织化学染色，并在食管发育异常患者（n = 30）或腺癌患者（n = 99）的食管标本中进行评估。评估的结构和病变包括正常食管（n = 88）、无发育异常的胃化生（n = 67）或肠化生（n = 51），以及低级别（n = 42）或高级别发育异常（n = 37）和食管腺癌（n = 99）。
我们在所有病变中均发现了TLR1、TLR2、TLR4和TLR6。TLR表达在巴雷特黏膜和发育异常中增加。从胃型到肠型柱状上皮，TLR表达显著增加。在癌症中，TLR4的高核染色和胞质染色与转移性疾病及不良预后相关。
在食管柱状上皮的恶性变化过程中，TLR1、TLR2、TLR4和TLR6上调。TLR4表达增加与食管腺癌的晚期阶段及不良预后相关。
