Patients with gastroesophageal reflux disease (n = 181) who underwent upper-gastrointestinal endoscopy with biopsies of the distal esophagus to rule out BE using HE/AB staining and CDX-2 immunostaining were followed for 3 years.
On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia.
CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers.
In conclusion, our study establishes a role for transcription factors SOX2 and CDX2 in the progression from gastric to gastrointestinal differentiation in Barrett's metaplasia.
Genomic DNA was extracted from blood samples collected from BE (n = 109) and GERD (n = 223) patients for genotyping of 5 SNPs each of Cdx1 and Cdx2 using TaqMan allelic discrimination assays.
The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies.
While Cdx2 is ectopically induced in the early metaplastic condition of Barrett's esophagus, its expression is not necessarily present in progressive Barrett's with dysplasia or adenocarcinoma.
The following on molecular mechanisms of Barrett's esophagus and adenocarcinoma contains commentaries on the mechanism of bile and gastric acid induced damage; the roles of BMP-4 and CDX-2 in the development of intestinal metaplasia; the transcription factors driving intestinalization in Barrett's esophagus; the contribution of bone marrow to metaplasia and adenocarcinoma; activation and inactivation of transcription factors; and a novel study design targeting molecular pathways in Barrett's esophagus.
Acid and bile salts induce CDX2 mRNA and protein expression in esophageal squamous cells from patients with Barrett's esophagus, but not from GERD patients without Barrett's esophagus.
These findings suggest that the inhibition of nucleostemin expression in "esophageal stem cells" in response to bile acid exposure may be involved in the pathogenesis of BE through upregulating CDX2 expression.
Relative to matched normal esophageal epithelia, CDX2 was overexpressed in esophagitis (37% for RNA; cytoplasmic immunoreactivity in 48% of tissues), a high proportion (91%) of BE tissues, and in EADC (57% for RNA; cell nuclear immunopositivity in 80%).
Caudal-related homeobox 2 (CDX2) is a transcription factor recently implicated in early differentiation and maintenance of normal intestinal epithelium and is suggested to play a key role in the pathogenesis of intestinal metaplasia in Barrett's esophagus.
The simultaneous up-regulation of both CDX2 and MUC2 after bile acid exposure provides molecular evidence of the role of bile acid in the pathogenesis of Barrett esophagus.