Toll-like receptor 9 expression in the natural history of Barrett mucosa.

Increased expression of TLR9 in esophageal adenocarcinoma and squamous cell carcinoma correlates with poor prognosis. We have explored the expression and suspected that TLR9 activation might contribute to pathogenesis in esophageal columnar metaplasia-dysplasia-neoplasia sequence, and hence, we have studied the usefulness of TLR9 as a marker for dysplasia. We have determined the expression of TLR9 in specimens with normal esophagus (n = 89), gastric (n = 71), or intestinal metaplasia (n = 56) without dysplasia, and low-grade (n = 51) or high-grade dysplasia (n = 40), and esophageal adenocarcinoma (n = 88). We observed linearly increasing TLR9 expression in specimens to be associated with change from normal epithelium to columnar metaplasia and further to dysplasia. ROC curve analysis showed clinically irrelevant sensitivity of 71% and specificity of 67% for TLR9 intensity in detection of low-grade dysplasia. Membrane-associated TLR9 expression detected by immunohistochemistry and immunofluorescence was predominantly associated with foveolar-type dysplasia as detected by HE staining (p = 0.015). TLR9 is expressed in Barrett's esophagus, and dissolution of TLR9 staining increases from nondysplastic epithelium to dysplastic. TLR9 may serve as a new way of recognizing the histopathological origin of dysplasia (adenomatous vs foveolar) with observed subcellular pattern of TLR9.