Esophageal Translational Research Laboratory
Tony E. Godfrey, PhD and Jeffrey H. Peters, MD
National Cancer Institute statistics report that 14,520 people will be diagnosed with esophageal cancer in 2005, and 13,570, or 93% are expected to die from it. Clearly, curing this disease is a challenge. Esophageal adenocarcinoma is the fastest growing cancer in the USA. Its primary risk factor is Barrett's esophagus (BE) which develops in a 10-15% of patients with gastroesophageal reflux disease.
The prevalence of Barrett's esophagus (BE), a premalignant epithelium and esophageal adenocarcinoma, have risen rapidly over the past two decades. Barrett's esophagus is characterized by the replacement of the normal esophageal squamous epithelium with a metaplastic epithelium resembling a more distal intestinal type. It is known to occur almost exclusively in patients with gastroesophageal reflux disease (GERD). The anatomy, physiology and reflux characteristics distinguishing patients with and without Barrett's esophagus were extensively investigated over the decades of the 1980's and 1990's. The presence of bile acids in the refluxed material has been consistently observed in patients with Barrett's esophagus strongly suggesting that they are important in its pathogenesis. The exact molecular mechanisms underlying this intestinal metaplastic and/or differentiation process remains largely unknown however.
Experimental studies have led to the widely accepted theory that Barrett's esophagus is an acquired metaplastic condition in which the stem cells of esophageal squamous epithelium or esophageal submucosal glands undergo altered differentiation leading to formation of intestinal columnar epithelium containing goblet cells. Although the molecular changes underlying the neoplastic development of Barrett-associated adenocarcinoma have been widely studied, little is known about the molecular pathways that induce and maintain the metaplastic process that is phenotypically seen as Barrett's esophagus. Recent evidence would suggest that a key step in the intestinal metaplasia characterizing Barrett's epithelium is the induction of a transcription factor known as CDX2.
Caudal-related homeobox 2 (CDX2) is a homeobox transcription factor that plays an important role in the early differentiation and maintenance of intestinal epithelium. Immunohistochemical staining studies have recently confirmed that CDX2 protein is overexpressed in human Barrett's epithelium, indicating that this intestinal transcription factor may be an early feature of intestinal metaplasia during the development of BE
The aim of the Department of Surgery esophageal translational research laboratory is to study the molecular pathogenesis of Barrett's epithelium including the signal transduction pathways involved in induction of CDX2 by components of gastroesophageal reflux. Elucidating the mechanisms and components involved may help in designing tests to detect the early onset of esophageal adenocarcinoma, identifying targets for treatment and potentially prevent the development of Barrett's esophagus in the population at risk.