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Overexpression of Stem Cell Markers Including Prominin 1/CD133 in Cardiac Mucosa and Barretts Intestinal Metaplasia
Dan Falkenback*1,3, Evgenii Borodachev1, Yuri V. Bobryshev1, Oliver M. Fisher1, Angelique Levert-Mignon1, Sarah J. Lord1,2, Melissa Thomas1,2, Reginald V. Lord1,2
1Gastro-Oesophageal Cancer Program, St Vincent's Centre for Applied Medical Research, Darlinghurst, NSW, Australia; 2Department of Surgery, Notre Dame University School of Medicine, Sydney, NSW, Australia; 3Department of Surgery, Lund University Hospital, Lund, Sweden

Introduction: It has been hypothesized that intestinal or other stem cells play an important role in the etiology of Barretts esophagus, and may influence endotherapy and other treatment outcomes. The aim of this preliminary study was to identify potential stem cell markers in the origin of this disease, focussing on cardiac mucosa and Barretts intestinal metaplasia (IM).
Material & Methods: Fresh frozen endoscopic biopsies from 30 patients were investigated. The mRNA relative expression levels of the putative stem cell markers PROM1/CD133, ABCG2, MSI1, ATXN1, MYC, KLF4, LGR5 and DCLK1 were measured using standard qRT-PCR methods in normal squamous (n=10), cardiac mucosa (n=10), and Barretts IM (n=10) tissues. The protein expression of Prominin-1/CD133 was measured by immunohistochemistry.
Results: Significant mRNA upregulation at the IM stage was found for ABCG2 and KLF4. An on/off pattern with highest expression in cardiac mucosa was seen for MSI1, ATXN1, LGR5, and DCLK1. PROM1/CD133 was not expressed in normal squamous epithelia but was progressively and highly overexpressed in cardiac mucosa and IM. Intense PROM1/CD133 protein expression was present in all goblet cells in IM.
Conclusions: This study identifies novel putative stem cell markers for this disease and provides some support for a role for non-intestinalised cardiac mucosa in the etiology of Barretts esophagus. PROMININ1/CD133 immunohistochemisty selectively stains goblet cells in IM, which may be valuable for the pathological interpretation of esophageal tissues.


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