MSI/MMR-deficient tumor diagnosis: Which standard for screening and for diagnosis? Diagnostic modalities for the colon and other sites: Differences between tumors
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Microsatellite instability (MSI), which is caused by deficiency of the DNA mismatch repair (MMR) system, is the molecular abnormality observed in tumors associated with Lynch syndrome. Lynch syndrome represents one of the most frequent conditions of cancer predisposition in human, thus requiring specific care and genetic counseling. Moreover, research has recently focused increasingly on MMR deficiency due to its positive predictive value for the efficacy of immune checkpoints inhibitors (ICKi) in metastatic tumors, regardless of their primary origin. MSI has also been demonstrated to constitute an independent prognostic factor in several tumor types, being also associated with alternative response to chemotherapy. These observations have led many professional medical organizations to recommend universal screening of all newly diagnosed colorectal cancers for dMMR/MSI status and increasing evidence support the evaluation of MSI in all human tumors regardless of the cancer tissue of origin. Currently, two standard reference methods, namely immunohistochemistry and polymerase chain reaction, are recommended for the detection of dMMR/MSI status. These methods are equally valid as the initial screening test for dMMR/MSI in colorectal cancer. To date, there is no recommendation for the detection of dMMR/MSI in other primary tumors. In this review, we will present a comprehensive overview of the methods used for evaluation of tumor dMMR/MSI status in colorectal cancer, as well as in other tumor sites. We will see that the evaluation of this status remains challenging in some clinical settings, with the need to improve the above methods in these specific contexts.
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Coexistence of the BRAFV600E mutation with deficient mismatch repair strongly suggests a sporadic tumor, obviating the need for oncogenetic referral.
“The coexistence of the BRAFV600E mutation with deficient mismatch repair (dMMR) strongly suggests a sporadic tumor, obviating the need for oncogenetic referral [47].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [47]
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Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
- Authors
- Svrcek, M., Lascols, O., Cohen, R., Collura, A., Jonchère, V., Fléjou, J.-F., Buhard, O., & Duval, A.
- Affiliations
- Inserm (FR)
- Sorbonne Université (FR)
- Corresponding author
- Svrcek, Magali
- Venue
- Bulletin du Cancer
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 106
- Issue
- 2
- Pages
- 119-128
- ISSN
- 0007-4551 (ISSN-L)
- OpenAlex
- W2912169856
- Cited by
- 90
- References
- 57
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 20 · 2023: 14 · 2022: 14 · 2021: 21 · 2020: 8 · 2019: 5
- FWCI
- 1.78
- Type
- journal article
- Language
- fr
- Open access
- bronze
- doi.org
- Licence
- Locations
- Bulletin du Cancer (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- microsatellite instability, mismatch repair deficiency, Lynch syndrome, colorectal cancer, immunohistochemistry, PCR, cancer susceptibility, immune checkpoint inhibitors, prognostic factors, cancer screening
- MeSH terms
- Algorithms, Colorectal Neoplasms, Hereditary Nonpolyposis, Humans, Immunohistochemistry, Mass Screening, Colorectal Neoplasms, Polymerase Chain Reaction, DNA Repair Enzymes, Microsatellite Instability, DNA Mismatch Repair
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