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Molekulare Pathologie des Magenkarzinoms

Molecular pathology of gastric cancer

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Zusammenfassung

Das Magenkarzinom ist weltweit die dritthäufigste Todesursache. Helicobacter-pylori- und Epstein-Barr-Virus-Infektionen, Ernährungsgewohnheiten sowie soziokulturelle Faktoren beeinflussen maßgeblich das Risiko für die Entstehung eines Magenkarzinoms. Kausal- und formalpathogenetisch werden mindestens drei verschiedene Typen unterschieden: das proximale Adenokarzinom (distaler Ösophagus und gastroösophagealer Übergang), das distale diffuse bzw. gering kohäsive und das distale intestinale Adenokarzinom. Genetische und epigenetische Alterationen betreffen zahlreiche Onkogene und Tumorsuppressorgene. Dabei ist insbesondere der onkogene kanonische WNT/β-Catenin-Signalweg dereguliert. Bei den hereditären und familiären Magenkarzinomen finden sich Keimbahnmutationen im CDH1-Gen und zahlreiche, die Krankheitssuszeptibilität beeinflussende, Genpolymorphismen. Molekulare Subtypen des Magenkarzinoms sind gefunden worden, die den diffusen vom intestinalen Typ unterscheiden und nicht vollständig konkordant sind mit dem Laurén-Phänotyp. Potenzielle Krebsstammzellmarker wurden identifiziert (z. B. ADAM17, CD133, FZD7, LGR5), deren Expression mit dem Patientenüberleben korreliert. Das Ansprechen auf unterschiedliche Chemotherapien scheint vom Tumortyp abzuhängen, womit die genotypisch basierte histologische Klassifikation des Magenkarzinoms zukünftig von größerer Bedeutung sein wird.

Abstract

Gastric cancer is one of the most common cancers worldwide. In recent decades, major advancements in the understanding of the epidemiology, pathology and pathogenesis of gastric cancer have been witnessed. Infections with Helicobacter pylori or Epstein-Barr virus, dietary and lifestyle factors contribute to the risk of developing gastric cancer. With respect to pathogenesis at least three distinct types of gastric cancer exist, (1) proximal, (2) distal diffuse and (3) distal non-diffuse types. Genetic and epigenetic alterations are related to oncogene mutations and tumor suppressor gene inactivation. Canonical oncogenic pathways such as the WNT/β-catenin signaling pathway are de-regulated in gastric cancer. Hereditary and familial type gastric cancers are currently linked to CDH1 gene mutations and various genetic polymorphisms determining disease susceptibility. Molecular subtypes of gastric cancer have been identified which separate diffuse from intestinal type gastric cancer and are not entirely congruent with the histopathological phenotype according to Laurén but may influence chemosensitivity. Putative cancer stem cell markers of gastric cancer have been found (e.g. ADAM17, CD133, FZD7, LGR5) and correlate with patient prognosis. Thus, molecular phenotyping of gastric cancer is still in its infancy and the search for novel diagnostic, prognostic and predictive biomarkers continues.

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Danksagung

Die Studien zum Magenkarzinom werden von der Deutschen Forschungsgemeinschaft unterstützt (Ro 1173/11 und Ro1173/12).

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Der korrespondierende Autor gibt für sich und seine Koautorin an, dass kein Interessenkonflikt besteht.

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  1. Institut für Pathologie, Christian-Albrechts-Universität Kiel, Arnold-Heller-Str. 3/14, 24105, Kiel, Deutschland

    C. Röcken & V. Warneke

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  1. C. Röcken
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  2. V. Warneke
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Correspondence to C. Röcken.

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Röcken, C., Warneke, V. Molekulare Pathologie des Magenkarzinoms. Pathologe 33 (Suppl 2), 235–240 (2012). https://doi.org/10.1007/s00292-012-1634-4

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