[563] Barrett's Esophagus in the Patients with Familial Adenomatous Polyposis

M Chen, C Snyder, L Hatcher, HT Lynch, P Watson, Z Gatalica. Creighton University School of Medicine, Omaha, NE

Background: Familial adenomatous polyposis (FAP) is caused by germ line mutations in APC gene. Patients with FAP are at high risk for development of colorectal carcinoma, but small intestinal cancers are the principal cause of death in patients who underwent prophylactic proctocolectomy. Sporadic Barrett's esophagus (BE) and Barrett's adenocarcinoma (BA) are intestinal type lesions of esophagus characterized by an early loss of heterozygosity at the APC locus. We hypothesized that patients with FAP are at risk for early development of BE or BA due to the inherited mutations in APC gene (haploinsufficiency).
Design: Upper gastrointestinal tract (UGI) biopsies from 36 patients with FAP were reviewed to determine the incidence of BE. The control group consisted of all non-FAP patients undergoing UGI endoscopic examination in our institution in the last 30 months. The difference in expression of Wnt pathway proteins' (APC, -catenin, E-cadherin and cyclin D1) in BE between BE⁺/FAP⁺, BE^-/FAP⁺ and age-matched BE⁺/FAP^- groups was studied using immunohistochemistry. Germline APC gene mutations were known in 24 patients.
Results: BE was found in six patients with history of FAP (6/36 or 16% vs. 266/1662 or 16% incidence in the control group). Average age of first diagnosis of BE in FAP patients was 37.8 years vs. 57.5 years in sporadic BE. Both classic FAP and attenuated FAP phenotypes were associated with BE .Two types of germ line mutations in APC gene were identified in BE⁺/FAP⁺ patients: Five patients had 2-base deletion in exon 4 (426delAT) and one patient had 4-base deletion in exon 15 (3202del4). No difference in Wnt signaling pathway proteins' expression was detected between BE⁺/FAP⁺ and the age matched group (n=10) of patients with sporadic BE (BE⁺/FAP^-).
Conclusions: Patients with FAP appear to be equally susceptible to the development of Barrett's esophagus as the general population, indicating that the primary effect of a common pathophysiologic mechanism (gastroesophageal reflux) underlies develoment of BE in FAP and in sporadic cases. However, Barrett's esophagus in FAP patients is detected on average 20 years earlier than in the general population. Although this early development of BE may indicate a predisposing effect of the germline APC gene mutations, early detection of BE is likely due to the endoscopic surveillance of FAP patients for the upper GI tract abnormalities.
Category: Gastrointestinal

Wednesday, March 11, 2009 1:00 PM

Poster Session VI # 98, Wednesday Afternoon