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MSI-Testung

Was ist neu? Was ist zu beachten?

MSI testing

What is new? What should be considered? German version

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Zusammenfassung

Aufgrund neuer Studiendaten mit Immuncheckpoint-Inhibitoren (ICI) gewinnt der Nachweis einer hochgradigen Mikrosatelliteninstabilität (MSI-H) bzw. der zugrunde liegenden Mismatch-Repair-Protein-Defizienz (dMMR) nun auch zur Prädiktion von Therapieansprechen zunehmend an Bedeutung. Aktuell wurde von der Europäischen Medizinischen Agentur (EMA) erstmals ein PD-1-ICI (Pembrolizumab) für die Erstlinientherapie des fortgeschrittenen (Stadium IV) dMMR/MSI‑H kolorektalen Karzinoms (KRK) zugelassen. Weitere Indikationen, wie z. B. für das metastastasierte dMMR/MSI-H-Endometriumkarzinom (EK) in der Zweitlinientherapie (Dostarlimab) sind bereits gefolgt, andere werden noch im laufenden Jahr 2021 erwartet. Dies erfordert eine Neubewertung der Frage nach der optimalen Testung in der Routinediagnostik. Auf Basis einer Abwägung von Stärken und Schwächen der in der Breite zur Verfügung stehenden Methoden (Immunhistochemie und PCR) wird ein Testalgorithmus vorgeschlagen, der qualitätsgesichert eine zuverlässige und kosteneffektive dMMR/MSI-H-Testung erlaubt. Für das KRK und EK ist damit analog internationaler Empfehlungen (NICE, NCCN) eine Testung bereits bei der Primärdiagnose möglich. Somit wird der Kliniker von vornherein in die Lage versetzt, neben den prädiktiven auch die prognostischen und prädispositionsbedingten Implikationen eines solchen Tests bei der Beratung von Patienten und Erarbeitung von Therapieempfehlungen zu berücksichtigen. Als Grundlage der Qualitätssicherung wird die Teilnahme an Ringversuchen und eine fortlaufende Ergebnisdokumentation (z. B. QuIP-Monitor) empfohlen.

Abstract

Based on new trial data regarding immune checkpoint inhibitors (ICIs), the detection of high-grade microsatellite instability (MSI-H) or underlying deficient mismatch repair protein (dMMR) is now becoming increasingly important for predicting treatment response. For the first time, a PD‑1 ICI (pembrolizumab) has been approved by the European Medicines Agency (EMA) for first-line treatment of advanced (stage IV) dMMR/MSI‑H colorectal cancer (CRC). Further indications, such as dMMR/MSI‑H endometrial carcinoma (EC), have already succeeded (Dostarlimab, 2nd line treatment) and others are expected to follow before the end of 2021. The question of optimal testing in routine diagnostics should therefore be re-evaluated. Based on a consideration of the strengths and weaknesses of the widely available methods (immunohistochemistry and PCR), a test algorithm is proposed that allows quality assured, reliable, and cost-effective dMMR/MSI‑H testing. For CRC and EC, testing is therefore already possible at the primary diagnosis stage, in line with international recommendations (NICE, NCCN). The clinician is therefore enabled from the outset to consider not only the predictive but also the prognostic and predispositional implications of such a test when counseling patients and formulating treatment recommendations. As a basis for quality assurance, participation in interlaboratory comparisons and continuous documentation of results (e.g., QuIP Monitor) are strongly recommended.

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Authors and Affiliations

  1. Institut für Pathologie Nordhessen, TARGOS Molecular Pathology GmbH, Germaniastr. 7, 34119, Kassel, Deutschland

    Josef Rüschoff

  2. Institut für Pathologie, Universitätsklinikum Carl Gustav Carus, Fetscherstr. 74, 01307, Dresden, Deutschland

    Gustavo Baretton & Korinna Jöhrens

  3. Institut für Pathologie, Universitätsklinikum Leipzig, Liebigstr. 26, Gebäude G, 04103, Leipzig, Deutschland

    Hendrik Bläker & Lars-Christian Horn

  4. Institut für Pathologie/Zentrum für molekularpathologische Diagnostik, Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Deutschland

    Wolfgang Dietmaier

  5. Institut für Pathologie, Campus Mitte, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland

    Manfred Dietel

  6. Pathologisches Institut, Universität Erlangen-Nürnberg, Krankenhausstr. 8–10, 91054, Erlangen, Deutschland

    Arndt Hartmann

  7. Pathologisches Institut, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, 80337, München, Deutschland

    Thomas Kirchner & Doris Mayr

  8. Institut für Pathologie, Universitätsklinikum RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland

    Ruth Knüchel

  9. Institut für Pathologie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    Sabine Merkelbach-Bruse & Reinhard Büttner

  10. Institut für Pathologie, Universitätsklinikum Essen, Hufelandstraße 55, 45147, Essen, Deutschland

    Hans-Ulrich Schildhaus

  11. Pathologisches Institut, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland

    Peter Schirmacher

  12. Institut für Hämatopathologie Hamburg, Fangdieckstr. 75a, 22547, Hamburg, Deutschland

    Markus Tiemann & Katharina Tiemann

  13. Institut für Pathologie, Technische Universität München, Trogerstr. 18, 81675, München, Deutschland

    Wilko Weichert

Authors
  1. Josef Rüschoff
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  2. Gustavo Baretton
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  3. Hendrik Bläker
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  7. Lars-Christian Horn
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  8. Korinna Jöhrens
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  9. Thomas Kirchner
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  10. Ruth Knüchel
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  13. Hans-Ulrich Schildhaus
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  14. Peter Schirmacher
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  15. Markus Tiemann
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  16. Katharina Tiemann
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  17. Wilko Weichert
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  18. Reinhard Büttner
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Correspondence to Josef Rüschoff.

Ethics declarations

Interessenkonflikt

S. Merkelbach-Bruse: Honorar für Vorträge und Advisory Boards von AstraZeneca, Roche, Novartis, GSK, MSD, Targos, Molecular Health und Merck. R. Büttner: Honorar für Vorträge und Advisory Boards von AbbVie, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Illumina, Lilly, MSD, Novartis, Qiagen, Pfizer und Roche. Mitgründer und Scientific Advisor von Targos Mol. Path. Gmbh. A. Hartmann: Honorar für Vorträge und Advisory Boards von Abbvie, AstraZeneca, Biontech, BMS, Boehringer Ingelheim, Cepheid, Diaceutics, Illumina, Ipsen, Janssen, MSD, Nanostring, Novartis, Qiagen, QUIP GmbH, Roche und 3DHistotech. L.-C. Horn: Honorar für Vorträge und Advisory Boards von AstraZeneca, Roche, Dako, Novartis, Exact Sciences und GSK. D. Mayr: Honorar für Vorträge und Advisory Boards von AstraZeneca, MSD, Roche, Novartis und BMS. R. Knüchel: Honorar für Vorträge und Advisory Board von MSD. J. Rüschoff: Honorar für Vorträge und Advisory Boards von MSD/Merck, GSK, BMS, AstraZeneca, Roche, Exact Sciences und QuIP GmbH. Mitgründer und medizin. Leiter von Targos Mol. Path. Gmbh. H.-U. Schildhaus: Honorar für Vorträge und Advisory Boards von MSD, BMS, Pfizer, Novartis Oncology, Roche Pharma und Molecular Health. Angestellter von Targos Mol. Path. Gmbh. W. Weichert: Honorar für Vorträge und Advisory Boards von Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, Amgen, Astellas, Illumina, Siemens, Agilent, GSK, ADC und Molecular Health. M. Tiemann: Honorar für Vorträge und Advisory Boards von BMS und MSD. G. Baretton, M. Dietel, K. Jöhrens, H. Bläker, W. Dietmaier, T. Kirchner, P. Schirmacher und K. Tiemann 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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Rüschoff, J., Baretton, G., Bläker, H. et al. MSI-Testung. Pathologe 42, 414–423 (2021). https://doi.org/10.1007/s00292-021-00944-7

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