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Diagnostic Pathology

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Open Access 01-12-2017 | Review

Molecular genetics of microsatellite-unstable colorectal cancer for pathologists

Authors: Wei Chen, Benjamin J. Swanson, Wendy L. Frankel

Published in: Diagnostic Pathology | Issue 1/2017

Abstract

Background

Microsatellite-unstable colorectal cancers (CRC) that are due to deficient DNA mismatch repair (dMMR) represent approximately 15% of all CRCs in the United States. These microsatellite-unstable CRCs represent a heterogenous group of diseases with distinct oncogenesis pathways. There are overlapping clinicopathologic features between some of these groups, but many important differences are present. Therefore, determination of the etiology for the dMMR is vital for proper patient management and follow-up.

Main body

Epigenetic inactivation of MLH1 MMR gene (sporadic microsatellite-unstable CRC) and germline mutation in an MMR gene (Lynch syndrome, LS) are the two most common mechanisms in the pathogenesis of microsatellite instability in CRC. However, in a subset of dMMR CRC cases that are identified by screening tests, no known LS-associated genetic alterations are appreciated by current genetic analysis. When the etiology for dMMR is unclear, it leads to patient anxiety and creates challenges for clinical management.

Conclusion

It is critical to distinguish LS patients from other patients with tumors due to dMMR, so that the proper screening protocol can be employed for the patients and their families, with the goal to save lives while avoiding unnecessary anxiety and costs. This review summarizes the major pathogenesis pathways of dMMR CRCs, their clinicopathologic features, and practical screening suggestions. In addition, we include frequently asked questions for MMR immunohistochemistry interpretation.

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Title: Molecular genetics of microsatellite-unstable colorectal cancer for pathologists
Authors: Wei Chen
Benjamin J. Swanson
Wendy L. Frankel
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2017
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-017-0613-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Molecular genetics of microsatellite-unstable colorectal cancer for pathologists

Abstract

Background

Main body

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Main body

Conclusion

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