The Complex, Clonal, and Controversial Nature of Barrett's Esophagus

Barrett's esophagus (BO) is a preneoplastic condition described as the replacement of the stratified squamous epithelium of the distal esophagus with one that histologically presents as a diverse mixture of metaplastic glands resembling gastric or intestinal-type columnar epithelium. The clonal origins of BO are still unclear. More recently, we have begun to investigate the relationship between the various metaplastic gland phenotypes observed in BO, how they evolve, and the cancer risk they bestow. Studies have revealed that glands along the BO segment are clonal units containing a single stem cell clone that can give rise to all the differentiated epithelial cell types in glands. Clonal lineage tracing analysis has revealed that Barrett's glands are capable of bifurcation and this facilitates clonal expansion and competition. In fact, BO in some patients appears to consist of multiple, independently initiated clones that compete with each other for space and possibly resources. This chapter discusses the concepts of clonal competition and expansion in BO and sets out to query what we know about the role of gland diversity and phenotypic evolution within this complex columnar metaplasia.