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Einfluss der Molekularpathologie auf die onkologische Chirurgie von Tumoren des oberen Gastrointestinaltraktes

Influence of molecular pathology on oncological surgery of tumors of the upper gastrointestinal tract

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Zusammenfassung

Hintergrund

In jüngster Vergangenheit konnten die Tumoren des oberen Gastrointestinaltraktes (ösophageales Plattenepithelkarzinom [ESCC], ösophageales Adenokarzinom [EAC], gastrales Adenokarzinom) zunehmend molekulargenetisch charakterisiert werden. Die resultierenden Subtypen bieten hierbei gemäß ihren biologischen Eigenschaften mögliche Angriffspunkte für zielgerichtete Therapien.

Ziel der Arbeit

Es wird eine Übersicht über den aktuellen Stand der molekularen Subtypen aller drei Tumorentitäten vermittelt und hiervon abgeleitete individualisierte Therapiestrategien diskutiert.

Material und Methoden

Es wurde eine selektive Literaturrecherche insbesondere hinsichtlich der bestehenden molekularen Subtypisierung, der derzeitig bestehenden „targeted therapies“ und der Auswirkung auf die onkologischen Therapiekonzepte durchgeführt. Dabei wurden Datenbanken wie PubMed genutzt.

Ergebnisse

Anhand der molekularen Charakteristika wird das ESCC in drei Subtypen kategorisiert. Genetisch ähnelt hierbei zumindest eine Subgruppe eher den Oropharynxkarzinomen als denjenigen des oberen Gastrointestinal(GI)-Traktes. Das EAC zeichnet sich dagegen durch seine hohe Tumorlast und die große chromosomale Instabilität aus. Beim Magenkarzinom werden zudem vier Subtypen unterschieden: 1. Epstein-Barr-Virus(EBV)-positive, 2. mikrosatelliteninstabile (MSI), 3. genomisch stabile (GS) und 4. chromosomal instabile (CIN) Tumoren.

Schlussfolgerung

Bisher konnten anhand der genetischen Charakterisierung nur wenige zielgerichtete Therapieoptionen für die drei Tumorentitäten in die tägliche Routine überführt werden. Hierzu gehören die selektive ERBB2-Inhibition, die Immuntherapie mittels PD-L1-Inhibition oder kombinierte Blockade von ERBB2/VEGF.

Abstract

Background

In the recent past tumors of the upper gastrointestinal (GI) tract, e.g. esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and gastric adenocarcinoma, have been increasingly characterized by molecular genetics. The resulting subtypes provide potential targets for novel targeted treatment based on the biological characteristics.

Objective

This article summarizes the current state of molecular subtyping in all three tumor entities and the individualized treatment strategies derived from these categories are discussed.

Material and methods

A selective literature search was performed focusing on molecular subtyping, current targeted treatment and the impact on the oncological treatment concepts. Databases such as PubMed were used.

Results

Based on molecular characteristics ESCC is nowadays categorized into three subtypes. Genetically, at least one subgroup resembles oropharyngeal carcinomas rather than those of the upper GI tract. In contrast, EAC is characterized by its high tumor burden and large chromosomal instability. In gastric carcinoma 4 subtypes are distinguished: 1) Epstein-Barr virus (EBV) positive, 2) microsatellite instability (MSI), 3) genomically stable (GS) and 4) chromosomally unstable (CIN) tumors.

Conclusion

To date, only a few targeted therapeutic options have been successfully transferred into daily routine derived from the genetic characterization of the three tumor entities. These include selective ERBB2 inhibition, immunotherapy using PD-L1 inhibition or combined blockade of ERBB2/VEGF.

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Authors and Affiliations

  1. Klinik und Poliklinik für Allgemein‑, Viszeral‑, Tumor- und Transplantationschirurgie, Uniklinik Köln, Kerpener Straße 62, 50937, Köln, Deutschland

    Patrick S. Plum, Hakan Alakus & Christiane J. Bruns

  2. Institut für Pathologie, Uniklinik Köln, Köln, Deutschland

    Alexander Quaas

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Correspondence to Patrick S. Plum.

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Interessenkonflikt

P.S. Plum, A. Quaas, H. Alakus und C.J. Bruns 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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Plum, P.S., Quaas, A., Alakus, H. et al. Einfluss der Molekularpathologie auf die onkologische Chirurgie von Tumoren des oberen Gastrointestinaltraktes. Chirurg 92, 981–985 (2021). https://doi.org/10.1007/s00104-021-01466-x

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