Expression Profiles of Cancer Stem Cell Markers: CD133, CD44, Musashi-1 and EpCAM in the Cardiac Mucosa—Barrett’s Esophagus—Early Esophageal Adenocarcinoma—Advanced Esophageal Adenocarcinoma Sequence

Publication date: Available online 30 December 2016
Source:Pathology - Research and Practice
Author(s): Anna Mokrowiecka, Lothar Veits, Christina Falkeis, Jacek Musial, Radzislaw Kordek, Mariusz Lochowski, Jozef Kozak, Agnieszka Wierzchniewska-Lawska, Michael Vieth, Ewa Malecka-Panas
INTRODUCTIONBarrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE − EAC sequence are not fully elucidated yet.AIMSWe used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression.METHODSImmunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies.RESULTSAll markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett's epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett's metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS).CONCLUSIONOur results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa.



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