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Hereditäres Magenkarzinom

Hereditary gastric cancer

Der Pathologe volume 31, pages 423–429 (2010)Cite this article

Zusammenfassung

Beim hereditären diffusen Magenkarzinom handelt es sich um ein autosomal-dominant vererbtes Tumorsyndrom mit 70–80%iger Penetranz. Das Lebenszeitrisiko, an einem klinisch manifesten Magenkarzinom zu erkranken, beträgt bei Frauen 63–83%, bei Männern 40–67%. Das Durchschnittsalter bei Diagnosestellung ist 40 Jahre. Betroffene Patienten besitzen in etwa 25–40% der Fälle eine Keimbahnmutation im CDH1-Gen. Dieses Gen kodiert für das Transmembranprotein E-Cadherin, das eine Schlüsselfunktion in der Zelladhäsion und in der Signaltransduktion einnimmt. Klassifiziert nach Laurén haben die Patienten ein multifokales diffuses Magenkarzinom mit Siegelringzellen und in späten Stadien eine Linitis plastica. Als Vorläuferläsionen kann ein siegelringzelliges In-situ-Karzinom in der Drüsenhalsregion, dem Sitz gastraler Stammzellen, gefunden werden. Charakteristisch sind Läsionen mit pagetoider Anordnung der Siegelringzellen unterhalb erhaltenem nichtneoplastischem Epithel. Die Anwendung einer PAS-Färbung erleichtert die Entdeckung kleinster Tumorherde. Der vorliegende Beitrag beleuchtet den Blickwinkel des Pathologen und den des Humangenetikers sowie das komplexe multidisziplinäre Management der Patienten.

Abstract

Hereditary diffuse gastric cancer is an autosomal dominant cancer syndrome with approximately 70%–80% penetrance. The cumulative lifetime risk of clinically detected gastric cancer is 63%–83% for women and 40%–67% for men. The average age at diagnosis is 40 years. Approximately 25%–40% of patients carry a germline mutation of the CDH1 gene. This gene encodes the transmembrane protein E-cadherin which plays a central role in cell adhesion and signal transduction. Classified according to Laurén, patients develop multifocal diffuse signet-ring cell carcinoma and, in late stages, linitis plastica. In the foveolar neck region, the site of gastric stem cells, in situ signet-ring cell carcinoma has been identified as a precursor lesion of invasive cancer. Therein, pagetoid spread of tumour cells below the preserved epithelium within the basal membrane represents the characteristic morphology. PAS staining may facilitate detection of tiny lesions.The present article provides detailed information on this cancer syndrome from the point of view of the pathologist as well as the human geneticist, focussing on the multidisciplinary management of affected patients.

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Authors and Affiliations

  1. Institut für Pathologie, Medizinische Universität Graz, Auenbruggerplatz 25, 8036, Graz, Österreich

    E.-M. Wolf &  C. Langner

  2. Institut für Humangenetik, Medizinische Universität Graz, Graz, Österreich

    J.B. Geigl

  3. Service d’anatomie et cytologie pathologique, Hôpital Saint-Antoine, Paris, France

    M. Svrcek

  4. Institut für Pathologie, Klinikum Bayreuth, Bayreuth, Deutschland

    M. Vieth

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  1. E.-M. Wolf
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  2. J.B. Geigl
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  3. M. Svrcek
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  4. M. Vieth
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  5. C. Langner
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Correspondence to C. Langner.

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Wolf, EM., Geigl, J., Svrcek, M. et al. Hereditäres Magenkarzinom. Pathologe 31, 423–429 (2010). https://doi.org/10.1007/s00292-010-1353-7

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