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Background <p>Adenocarcinomas of the upper gastrointestinal (GI) tract are among the most common cancers with significant morbidity and mortality worldwide. A&#xa0;molecular understanding of these tumors is essential for the development and application of targeted therapies.</p> Objectives <p>This work aims to describe the molecular characteristics of adenocarcinomas of the upper GI tract in particular and shows their relevance for the determination and interpretation of therapeutically relevant biomarkers as a&#xa0;basis for personalized treatment concepts.</p> Materials and methods <p>The significance of molecular subtypes of GI adenocarcinomas for diagnostics and therapy was analyzed based on current guidelines and studies (PubMed research, U.S. National Library of Medicine, Bethesda, MD, USA).</p> Results <p>Among gastrointestinal adenocarcinomas of the upper GI tract, five molecular subtypes were identified (Epstein-Barr virus [EBV], microsatellite instability [MSI], hypermutated single nucleotide variants [HM-SNV], chromosomal instability [CIN], genomically stable [GS]), from which therapeutically relevant alterations can be derived. These findings have led to the development of new diagnostic tests and targeted drugs that enable individualized therapy.</p> Conclusions <p>If systemic therapy is required, adenocarcinomas of the upper GI tract must be analyzed for the presence of biomarkers with varying degrees of expression in terms of personalized therapy options. These routinely include mismatch-repair protein/microsatellite status, PD-L1, Her2/neu and Claudin18.2. These analyses are primarily conducted on tumor tissue using immunohistochemistry and possible complementary molecular techniques and require close collaboration between diagnostic pathology and clinical oncology.</p>

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Fortschritte in der molekularen Diagnostik und Therapie von Adenokarzinomen des oberen Gastrointestinaltrakts

  • 期刊论文

  • 发表日期：

    2025年5月9日

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  • Paul Steiner,
  • Markus Möhler,
  • Yvonne Huber,
  • Alexander Quaas

摘要

Background

Adenocarcinomas of the upper gastrointestinal (GI) tract are among the most common cancers with significant morbidity and mortality worldwide. A molecular understanding of these tumors is essential for the development and application of targeted therapies.

Objectives

This work aims to describe the molecular characteristics of adenocarcinomas of the upper GI tract in particular and shows their relevance for the determination and interpretation of therapeutically relevant biomarkers as a basis for personalized treatment concepts.

Materials and methods

The significance of molecular subtypes of GI adenocarcinomas for diagnostics and therapy was analyzed based on current guidelines and studies (PubMed research, U.S. National Library of Medicine, Bethesda, MD, USA).

Results

Among gastrointestinal adenocarcinomas of the upper GI tract, five molecular subtypes were identified (Epstein-Barr virus [EBV], microsatellite instability [MSI], hypermutated single nucleotide variants [HM-SNV], chromosomal instability [CIN], genomically stable [GS]), from which therapeutically relevant alterations can be derived. These findings have led to the development of new diagnostic tests and targeted drugs that enable individualized therapy.

Conclusions

If systemic therapy is required, adenocarcinomas of the upper GI tract must be analyzed for the presence of biomarkers with varying degrees of expression in terms of personalized therapy options. These routinely include mismatch-repair protein/microsatellite status, PD-L1, Her2/neu and Claudin18.2. These analyses are primarily conducted on tumor tissue using immunohistochemistry and possible complementary molecular techniques and require close collaboration between diagnostic pathology and clinical oncology.