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Interleukin-17 Expression in the Barrett’s Metaplasia-Dysplasia-Adenocarcinoma Sequence

DOI: 10.5402/2012/578149

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Abstract:

Introduction. This pilot study evaluated the expression of the proinflammatory cytokine IL-17 along the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence by establishing the expression levels of IL-17 in columnar epithelium, intestinal metaplastic cells, and dysplastic/glandular neoplastic cells. Immunohistochemical techniques were used to examine the accumulation of the proinflammatory cytokine IL-17 in forty ( ) formalin-fixed, paraffin-embedded oesophageal archived specimens across a range of endoscopic diagnostic categories, and a highly significant difference was found, where , in IL-17 expression (Kruskall Wallis and Mann-Whitney ) between all the cell types examined. There was also a strong positive correlation (Spearman's rank correlation) between disease progression and IL-17 expression ( , , ), IL-17 expression was absent or absent/weak in columnar epithelium, weak to moderate in columnar metaplastic cells, and moderate to strong in dysplastic/neoplastic cells, which demonstrated that the elevation of IL-17 expression occurs in the progression of the disease. Understanding the differential expression of IL-17 between benign and malignant tissue potentially has a significant diagnostic, prognostic, and therapeutic value. Ultimately, this selective biomarker may be employed in routine clinical practice for the screening of oesophageal adenocarcinoma. 1. Introduction Oesophageal Adenocarcinoma (OAC) is the focus of intense research into the cause of the disease and treatment [1]. In the context of OAC screening, a biomarker capable of reliably predicting progression to dysplasia or cancer by increased expression is highly valuable [2]. Oesophageal cancer develops symptoms late in the course of this disease and carries a poor prognosis. In the UK, oesophageal cancer is the eleventh most commonly diagnosed cancer and, of greater concern, the sixth most common cause of death from cancer, which represented 1?:?20 of all cancer deaths in the UK; 8,161 new cases were diagnosed in 2009 and the mortality rate was 7,610 in 2010 [3]. The role of inflammation in the development of OAC is not well understood, unlike its role in colon and breast cancers. However, this role in the progression of OAC is now beginning to gain greater attention [4]. Proinflammatory cytokines and their pathways are associated with inflammation in Barrett’s oesophagus and tumourigenesis. Elucidating the association between inflammation and OAC may contribute to the eventual prevention of OAC [5]. Further assessment of these cytokines has recently been recommended, as these may

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