Testing for deficient mismatch repair and microsatellite instability: A focused update

Rüschoff J, Schildhaus HU, Rüschoff JH, Jöhrens K, Bocker Edmonston T, Dietmaier W, Bläker H, Baretton G, Horst D, Dietel M, Hartmann A, Klauschen F, Merkelbach-Bruse S, Stenzinger A, Schöniger S, Tiemann M, Weichert W, Büttner R (2023)

Publication Type: Journal article, Review article

Publication year: 2023

Journal

Die Pathologie Springer

Book Volume: 44

Pages Range: 61-70

DOI: 10.1007/s00292-023-01208-2

Abstract

Testing to detect mismatch repair deficiency (dMMR) and high-grade microsatellite instability (MSI-H) has become an integral part of the routine diagnostic workup for colorectal cancer (CRC). While MSI was initially considered to be a possible indicator of a hereditary disposition to cancer (Lynch syndrome, LS), today the prediction of the therapy response to immune checkpoint inhibitors (ICI) is in the foreground. Corresponding recommendations and testing algorithms are available for use in primary diagnosis (reviewed in: Rüschoff et al. 2021).Given the increasing importance for routine use and the expanding indication spectrum of ICI therapies for non-CRCs, such as endometrial, small intestinal, gastric, and biliary tract cancers, an updated review of dMMR/MSI testing is presented. The focus is on the challenges in the assessment of immunohistochemical stains and the value of PCR-based procedures, considering the expanded ICI indication spectrum. A practice-oriented flowchart for everyday diagnostic decision-making is provided that considers new data on the frequency and type of discordances between MMR-IHC and MSI-PCR findings, and the possible role of Next Generation Sequencing in clarifying them. Reference is made to the significance of systematic quality assurance measures (e.g., QuIP MSI portal and multicenter proficiency testing), including regular continued training and education.

Authors with CRIS profile

Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Universitätsspital Zürich (USZ) CH Switzerland (CH) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Cooper University Hospital US United States (USA) (US) Universität Regensburg DE Germany (DE) Universitätsklinikum Leipzig DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Rüschoff, J., Schildhaus, H.U., Rüschoff, J.H., Jöhrens, K., Bocker Edmonston, T., Dietmaier, W.,... Büttner, R. (2023). Testing for deficient mismatch repair and microsatellite instability: A focused update. Die Pathologie, 44, 61-70. https://dx.doi.org/10.1007/s00292-023-01208-2

MLA:

Rüschoff, Josef, et al. "Testing for deficient mismatch repair and microsatellite instability: A focused update." Die Pathologie 44 (2023): 61-70.

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