1. Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus
Pathobiology 2017;84: DOI: /
Fig. 1.a BE develops via conversion of the normal, squamous esophageal epithelium (NE) into an intestinal columnar epithelium. Some pathology societies demand the presence of goblet cells for BE diagnosis (see Introduction). BE lesions may proceed via dysplastic states, also called intraepithelial neoplasia (IEN), with frequent loss of goblet cells, to BAC. b These fundamental changes in histological architecture are possibly more understandable via an analogy: skyscrapers represent the normal esophageal squamous epithelium with its different layers, and these are then turned into little town houses via unknown mechanisms, representing the BE lesions with columnar epithelium.
© 2016 S. Karger AG, Basel

2. Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus
Pathobiology 2017;84: DOI: /
Fig. 2. Potential routes to the development of BE. The exact mechanisms by which the normal esophageal squamous epithelium is turned into BE have not been well elucidated. However, 4 potential development routes have been described so far: the trans-differentiation (1) and trans-commitment of stem cells of either esophageal (2) or bone marrow origin (3) and cellular competition (4). Each of this hypotheses may explain the development of BE lesions and may depend on the background of the individual patient.
© 2016 S. Karger AG, Basel

3. Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus
Pathobiology 2017;84: DOI: /
Fig. 3. Changes during the development of BE. The exact events initiating the development of BE are still largely unknown. However, changes in the microenvironment such as increased acid levels due to reflux or chemokine expression are known to initiate BE lesions. Moreover, key transcription factors like CDX-2 are upregulated, which then mediates complex changes in the epigenetic landscape including promoter demethylation or miRNA alterations. This leads, finally, to gene/protein expression changes associated with differentiation programs and the subsequent upregulation of columnar markers (e.g. keratin-7).
© 2016 S. Karger AG, Basel