The GCTM-5 Monoclonal Antibody Is a Biomarker for Progenitors in the Columnar Lined Esophagus
DR Braxton, LM Petrovic, PT Chandrasoma, MF Pera. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Los Angeles; Los Angeles; Keck School of Medicine of the University of Southern California, Los Angeles
Background: Barrett's esophagus (BE) is a premalignant condition characterized by the presence of Intestinal Metaplasia (IM). The exact pathogenesis and cell of origin of IM has not been elucidated. Recently, a multilayered epithelium has been proposed to be the precursor of IM. The GCTM-5 monoclonal antibody reacts with adult tissues derived from the foregut endoderm such as the pancreatic and biliary ductal epithelium but not with normal gastric or esophageal mucosa. The purpose of this study is to evaluate the ability of the GCTM-5 antibody to identify a progenitor population in the reflux-induced metaplasia to adenocarcinoma sequence of BE.
Design: A total of 20 biopsy specimens from patients who had undergone evaluation for GERD and were categorized as containing foci of Cardiac mucosa (CM), Intestinal metaplasia (IM), Dysplasia (D), and Adenocarcinoma (EAC). The proliferative and maturation characteristics (Sialo- versus Sulphomucin) of the GCTM-5 reactive epithelia were assessed by Ki-67 and the High Iron Diamine /Alcian Blue (HID/AB) biochemical stain.
Results: GCTM-5 did not react with squamous epithelium. GCTM-5 marked a subpopulation of cells in cardiac mucosa (3/8) and intestinal metaplasia (14/14) foci, and was more widely reactive in areas of dysplasia (5/7) and adenocarcinoma (3/5). GCTM-5 was also reactive with multilayered epithelium (2/4) and focally reactive with the ductal epithelium of submucosal glands. Histochemical evaluation of mucin characteristics using the HID/AB method found that GCTM-5 was expressed to a high degree of concordance with sialomucins. Cells that failed to react with HID/AB did not react with GCTM-5. The ME was found to be proliferating in 100% of the GCTM-5+ foci. The GCTM-5+ CM was found to be proliferating in 83% of foci. Foci of GCTM-5+ IM were proliferating in 94% of foci.
Conclusions: Our data indicate that the GCTM-5+ epithelia are proliferative and immature as evidenced by Ki-67 and sialomucin co-staining respectively. This suggests that GCTM-5 marks progenitors of the metaplastic epithelia in the esophagus. Therefore, we propose that the GCTM-5+ Multilayered epithelium is a multipotent progenitor of the metaplastic epithelia found in the esophagus. These finding contribute to the understanding of the pathogenesis BE and may lead to the use of GCTM-5 as a diagnostic or prognostic biomarker.
Monday, March 22, 2010 8:15 AM
Platform Session: Section E, Monday Morning