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Pathophysiologie des Adenokarzinoms am ösophagogastralen Übergang (AEG)

Pathophysiology of adenocarcinoma of the esophagogastric junction (AEGJ)

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Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Der Barrett-Ösophagus wird als entscheidende Ursprungsläsion für das Adenokarzinom am ösophagogastralen Übergang (AEG) angesehen.

Weitgehend unklar ist allerdings nach wie vor, welche Faktoren, Einwirkungen und Abläufe für die Karzinogenese verantwortlich sind.

Fragestellung

In dieser Übersichtsarbeit sollen v. a. die Bedeutung epidemiologischer, genetischer und immunologischer Faktoren sowie der Einfluss eines hierdurch teilweise veränderten Mikromilieus als initiierende Faktoren erörtert werden.

Ergebnisse

Veränderungen in Mikrobiom und Genstruktur (z. B. durch Verlust von TP53 und p16) können eine Nische von Stammzellen am ösophagogastralen Übergang (die z. B. in Mäusen LGR5, CCK2R und CAR4 exprimieren) bilden, in der vermehrte Zellteilung sowie eine maligne Entartung begünstigt wird. Dabei könnten spezifische Stammzellen, die wahrscheinlich aus Drüsen im Bereich der Kardia im Magen entstehen − als Ursprung für die maligne Transformation sowie in Abhängigkeit von ihrem Differenzierungspotenzial für die Tumorentstehung ausschlaggebend sein. Aktuelle Studien deuten darauf hin, dass das metaplastische Epithel nicht im Ösophagus, sondern in der Kardia entsteht, von wo Stammzellen (im weiteren Verlauf) in den Ösophagus expandieren.

Schlussfolgerungen

Ein besseres Verständnis dieser Mechanismen kann zu einer besseren Früherkennung, Prävention und schlussendlich auch Therapie der AEG führen.

Abstract

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.

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  1. Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Deutschland

    L. Liotta &  M. Quante

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  1. L. Liotta
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Correspondence to L. Liotta or M. Quante.

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L. Liotta und M. Quante geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Liotta, L., Quante, M. Pathophysiologie des Adenokarzinoms am ösophagogastralen Übergang (AEG). Onkologe 25, 1055–1064 (2019). https://doi.org/10.1007/s00761-019-00666-9

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