Pathophysiologie des Adenokarzinoms am ösophagogastralen Übergang (AEG)

Background: Barrett esophagus is defined as the decisive precursor lesion for the development of adenocarcinoma of the esophagogastric junction (AEGJ); however, little is known about the risk factors and mechanisms which are responsible for the carcinogenesis. Objective: In this review the importance of epidemiological, genetic and immunological factors as well as the impact of the microenvironment as initiating factors in the development of AEGJ are discussed. Results: Alterations in genomic structure (e.g. due to the loss of TP53 or p16) and the microbiome could lead to the development of a niche of stem cells in the gastroesophageal junction (e.g. labeled by LGR5, CCK2R and CAR4 in mice) that encourage a faster cell division and malignant transformation. Specific stem cells, probably originating from cardiac glands of the stomach, could be responsible for the malignant transformation and, depending on the differentiation pattern, could be crucial for the carcinogenesis. The results of current studies indicate that the metaplastic epithelium arises not in the esophagus but in the cardia and in the further course the stem cells expand from there into the esophagus. Conclusion: A better understanding of the mechanisms by which normal squamous epithelium progresses to early stage invasive cancer will help formulate rational surveillance guidelines and allow resources to be diverted away from patients at low risk of malignancy.