MSI-Testung

Rüschoff, Josef; Baretton, Gustavo; Bläker, Hendrik; Dietmaier, Wolfgang; Dietel, Manfred; Hartmann, Arndt; Horn, Lars‐Christian; Jöhrens, Korinna; Kirchner, Thomas; Knüchel, Ruth; Mayr, Doris; Merkelbach‐Bruse, Sabine; Schildhaus, Hans–Ulrich; Schirmacher, Peter; Tiemann, Markus; Tiemann, Katharina; Weichert, Wilko; Büttner, Reinhard

doi:10.1007/s00292-021-00944-7

Cited by 8 publications

(9 citation statements)

References 46 publications

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“…Our previous recommendation of a step-by-step MMR/MSI diagnosis [ 22 ], starting with two MMR antibodies (PMS2, MSH6), is updated below, taking new data and recommendations into account [ 4 , 10 , 20 , 31 ]. The focus will be on the challenges of MMR/MSI testing in everyday diagnostics, resulting from the expanded ICI therapy indication spectrum, culminating in the proposal of an optimized testing algorithm.…”

Section: Significance Of Mmr-ihc and Msi-pcr In Different Organ Systemsmentioning

confidence: 99%

“…In other tumor entities the percentage of concordant dMMR and MSI‑H findings was only 79%. Accordingly, outside the colon, PCR is less sensitive and a stepwise approach starting with MMR-IHC is recommended in practice ([ 4 , 31 ], review in: [ 22 ]).…”

Section: Classic Dmmr Findingsmentioning

confidence: 99%

“…*) Participation in multicenter proficiency testing, e.g., QuIP (https://www.quip.eu/de), is recommended. **Two-antibody approach sufficient for classic dMMR and normal findings [ 22 ]. ***In the event of a loss of MLH1, the lack of promoter methylation (or the lack of BRAF mutation in case of CRC) indicates possible LS.…”

Section: Unusual Dmmr Findingsmentioning

confidence: 99%

“…The MMR analysis process begins with optimum fixation of the tissue to be investigated and the consideration of pre-analytical factors [ 18 ]. Optimally fixed samples are essential for detecting diagnostically relevant loss of staining, which is why biopsies should be favored over resected tissue whenever possible [ 7 , 22 ]. Internal staining controls with evidence of a good-to-strong immunohistochemical reaction in the normal tissue are required for confident interpretation.…”

Section: Update On Step-by-step Assessment Of Mmr-ihcmentioning

confidence: 99%

“…Testing for deficient mismatch repair (dMMR) with consecutive high-grade microsatellite instability (MSI-H) used to be primarily recommended for patients with conspicuous family histories suggestive of a possible hereditary tumor disposition syndrome such as Lynch syndrome (LS) and related syndromes, especially in colorectal cancer (CRC) and endometrial cancer (EC). With the evidence that tumors of the dMMR/MSI‑H type demonstrate a high response rate to immune checkpoint inhibitors (ICI; [ 14 ]), the recommendation for universal testing of all CRC and EC already at the stage of the primary diagnosis has recently made its way into the corresponding therapy guidelines on a national and international level ([ 2 ], overview in [ 22 ]). In 2021, the European Medicines Agency (EMA) approved two PD‑1 targeted ICIs with pembrolizumab as first line for metastasized CRC [ 1 ], and dostarlimab as second line for recurrence or therapy failure for EC [ 21 ].…”

mentioning

confidence: 99%

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Testing for deficient mismatch repair and microsatellite instability

Rüschoff,

Schildhaus,

Rüschoff

et al. 2023

Pathologie

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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.

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