898 Title: Insulin Like Growth Factor (IGF) Signaling Pathway in Barrett's Esophagus (BE)

Abstract

Background: Little is known regarding the role of mucosal and submucosal glands in the development of Barrett's esophagus (BE). Some studies have suggested that mucosal and/ or submucosal glands, and their ducts, may contain precursor stem cells for BE. Unfortunately, previous studies that have evaluated glands in BE did not always specify the type or location of these structures. The aim of this study was to evaluate the pathologic features of mucosal and submucosal glands in BE in order to gain insight into their role in the pathogenesis of this condition. Design: Routinely processed tissue sections from 112 patients with BE (64 patients with biopsies only, 48 with resection specimens) and 32 non-BE controls (9 esophageal resections, 23 autopsies) were evaluated for the number and location of glands, and for their association with the type of overlying epithelium. BE patients with biopsies were separated into no (i.e. esophageal columnar metaplasia without goblet cells), low, high, and very high density goblet cell groups based on predetermined criteria. Immunostaining for p63, a peptide known to be present in basal squamous cells, including stem cells, was performed on a subset of BE biopsies. Results: Submucosal glands were nearly significantly increased in prevalence in non-BE controls (resections and autopsies) versus BE resection specimens (mean # glands per tissue section: 2.5 vs. 1.4, p=0.08). Mucosal glands were present in 86% of BE resections, but in none of the control esophageal resections or autopsies without BE, except at the distal GEJ. In BE biopsies, mucosal glands were present in 66% of cases, but showed a highly significant decrease in number from no (89%), to low (44%), to high (21%), and very high (7%) goblet cell density BE subgroups (p<0.001). P63 was positive in 43 % of glands overall, and it was significantly more common in glands of “BE” cases without goblet cells (p<0.01). Finally, a strong significant association was also noted between the presence of non-goblet columnar epithelium including multilayered epithelium overlying mucosal glands in all patients, regardless of the patients' goblet cell density (p<0.001). Conclusions: Increased submucosal glands may play a protective role in the prevention of BE. Our data also suggests that mucosal glands are metaplastic in origin, may be derived from the adjacent basal cell layer of squamous epithelium, and probably give rise to early non-goblet columnar metaplasia in patients developing BE.