title: 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.
abstract: BACKGROUND
  Barrett'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.
  
  
  OBJECTIVE
  We used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression.
  
  
  METHODS
  Immunohistochemistry 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.
  
  
  RESULTS
  All 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. Electronic address: annazlo@wp.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Mokrowiecka
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Veits
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Falkeis
authors.affiliation: Department of Pathology, Chair of Oncology, Medical University of Lodz, Lodz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Musial
authors.affiliation: Department of Pathology, Chair of Oncology, Medical University of Lodz, Lodz, Poland.
authors.forename: Radzislaw
authors.initials: R
authors.lastname: Kordek
authors.affiliation: Departmantof Chest Surgery and Respiratory Rehabilitation, Medical University of Lodz, Lodz, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Lochowski
authors.affiliation: Departmantof Chest Surgery and Respiratory Rehabilitation, Medical University of Lodz, Lodz, Poland.
authors.forename: Jozef
authors.initials: J
authors.lastname: Kozak
authors.affiliation: Department of Pathology, Medical University of Lodz, Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wierzchniewska-Lawska
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.affiliation: Department of Pathology, Chair of Oncology, Medical University of Lodz, Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Malecka-Panas
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D018960:Hyaluronan Receptors; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins
keywords: Barrett’s esophagus; CD133; CD44; EpCAM; Esophageal cancer; Neoplastic stem cells