Barrett’s esophagus in the patients with familial adenomatous polyposis

Abstract

Familial adenomatous polyposis (FAP) is caused by germ line mutations in the APC gene. Barrett's esophagus (BE) and Barrett's adenocarcinoma are intestinal type lesions of the esophagus characterized by an early loss of heterozygosity at the APC locus. We hypothesized that patients with FAP are at risk for the early development of BE due to the inherited mutations in the APC gene (haploinsufficiency). Upper gastrointestinal (UGI) tract biopsies from 36 patients with FAP were reviewed to determine the incidence and characteristics of BE in these patients. Twenty-four patients were confirmed carriers of a deleterious germline APC mutation. The other 12 patients were from FAP families with known APC gene mutations and had clinical manifestations of FAP. The control group consisted of patients who did not have a personal or family history of FAP undergoing UGI endoscopic examination in our institution over a 30 month period of time. The difference in expression of Wnt pathway proteins (APC, β-catenin, E-cadherin and cyclin D1) in BE between BE(+)/FAP(+), BE(-)/FAP(+) and age-matched BE(+)/FAP(-) groups was studied using immunohistochemistry. BE was found in 6 of 36 (6/36 or 16%) patients with FAP and in 266 of 1662 patients (16%) in the control group of symptomatic patients. The average age at the first diagnosis of BE in FAP patients was 37.8 versus 57.5 years in the control group (sporadic BE). When compared to age matched BE(+)/FAP- group (7/334), patients with FAP had a significantly (p = 0.005843, odds ratio 9.2; Fisher exact test) higher incidence of 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 of patients with sporadic BE (BE(+)/FAP(-)). Patients with FAP appear to have increased risk for the development of BE, which on average develops some 20 years earlier than in patients without FAP. This association needs to be taken in account when caring for the patients with FAP.