Dataset Information

[Testing deficient mismatch repair and microsatellite instability : A focused update. German version].

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.

SUBMITTER: Ruschoff J

PROVIDER: S-EPMC10457237 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

[Testing deficient mismatch repair and microsatellite instability : A focused update. German version].

Rüschoff Josef J Schildhaus Hans-Ulrich HU Rüschoff Jan Hendrik JH Jöhrens Korinna K Bocker-Edmonston Tina T Dietmaier Wolfgang W Bläker Hendrik H Baretton Gustavo G Horst David D Dietel Manfred M Hartmann Arndt A Klauschen Frederick F Merkelbach-Bruse Sabine S Stenzinger Albrecht A Schöniger Sandra S Tiemann Markus M Weichert Wilko W Büttner Reinhard R

Pathologie (Heidelberg, Germany) 20230807 5

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 pri ...[more]

PMID: 37548948

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Project description:BackgroundIn 2017, DNA mismatch repair/microsatellite instability (MMR/MSI) testing was nationally recommended for advanced colorectal cancers based on favorable immune checkpoint inhibitor responses among patients with MMR-deficient/MSI-high tumors.MethodsPatients ages ≥20-years-old presenting with stage IV colorectal adenocarcinoma from 2010 to 2017 were identified from the National Cancer Database. 2017 was the latest year with available testing utilization data. Patient, tumor, socioeconomic, and care setting characteristics were evaluated for association with upfront MMR/MSI testing in 2017 using multivariable logistic regression and average adjusted predicted probabilities (%AAP).ResultsAmong 72,830 stage IV colorectal cancers, upfront MMR/MSI testing levels increased from 16.4% in 2010 to 56.4% in 2017. For patients diagnosed in 2017 (i.e., following national recommendations, n = 10,022), testing levels were lower for older patients (Padj < 0.001), and were independent of patients' race/ethnicity and insurance status. Patients from the poorest quartile of households received less testing [49.6%AAP, 99.9% confidence interval (CI) 45.5-53.7] than patients from the 3rd (56.9%AAP, 99.9% CI, 53.3-60.6; Padj < 0.001) or 4th quartiles (57.6%AAP, 99.9% CI, 54.3-60.9; Padj < 0.001). Although testing levels improved most at community programs, they remained lower in 2017 (46.6%AAP, 99.9% CI, 41.0-52.1) compared with academic/NCI-designated comprehensive cancer centers (62.8%AAP, 99.9% CI, 59.7-65.8; Padj < 0.001).ConclusionsUpfront MMR/MSI testing utilization for patients with advanced colorectal cancer has increased but there is still substantial need for optimization. Testing utilization disproportionately lagged for patients who were older, from the poorest quartile of households, or managed at community cancer programs.ImpactOur findings indicate opportunities for improving rates of MMR/MSI testing and reporting, possibly through incorporation into quality control and accreditation metrics.

Dataset Information

[Testing deficient mismatch repair and microsatellite instability : A focused update. German version].

Publications

[Testing deficient mismatch repair and microsatellite instability : A focused update. German version].

Similar Datasets

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