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Open questions in oesophageal adenocarcinogenesis
  1. Carlo C Maley
  1. Correspondence to:
    Dr C C Maley
    Molecular and Cellular Oncogenesis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA; cmaley{at}

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Transition from GORD to Barrett’s oesophagus, and possibility of a reversal mechanism

Barrett’s oesophagus develops as a complication of chronic gastro-oesophageal reflux disease (GORD), and is the only known precursor to oesophageal adenocarcinoma (EA). Barrett’s oesophagus is an ideal model for studying neoplastic progression, because it can be studied longitudinally in vivo, with protocols that allow for safe, reproducible sampling by endoscopy biopsies.1 Furthermore, the major genetic events that characterise progression in Barrett’s oesophagus are some of the most common genetic events across human neoplasms, including inactivation of the tumour suppressor genes p16 (CDKN2A/INK4A)2,3 and p53 (TP53),4,5 with the subsequent development of tetraploidy and aneuploidy.6,7,8,9,10

There are important open questions at all stages of progression from GORD to EA. Little is known about the transition from GORD to Barrett’s oesophagus. What is the cell of origin for Barrett’s oesophagus? And why do only a minority of patients with GORD undergo that transition? The presence of p16, p53 and ploidy lesions in a Barrett’s neoplasm makes it very likely to progress to cancer,11 but the complete set of necessary and sufficient molecular events for carcinogenesis are not yet defined. The difficulty in treating EA has long been a problem without any solution, and so attention has been turned to prevention of EA. Non-steroidal anti-inflammatory drugs11,12

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  • Competing interests: None.

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