Microsatellite Instability in Colorectal Cancer

Boland, C. Richard; Goel, Ajay

doi:10.1053/j.gastro.2009.12.064

Cited by 2,456Genetic factors in colorectal cancerColorectal Cancer Treatments and StudiesColorectal Cancer Surgical Treatments

Microsatellite Instability in Colorectal Cancer

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Boland, C. Richard, Goel, Ajay·2010·Gastroenterology

DOI 10.1053/j.gastro.2009.12.064PMC PMC3037515

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Abstract

Microsatellite instability (MSI) is a hypermutable phenotype caused by the loss of DNA mismatch repair activity. MSI is detected in about 15% of all colorectal cancers; 3% are of these are associated with Lynch syndrome and the other 12% are caused by sporadic, acquired hypermethylation of the promoter of the MLH1 gene, which occurs in tumors with the CpG island methylator phenotype. Colorectal tumors with MSI have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrate, and a poorly differentiated, mucinous or signet ring appearance. They have a slightly better prognosis than colorectal tumors without MSI and do not have the same response to chemotherapeutics. Discovery of MSI in colorectal tumors has increased awareness of the diversity of colorectal cancers and implications for specialized management of patients.

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MSI is commonly identified through separate MSI analysis and/or additional immunohistochemical staining for mismatch repair enzymes in pathology diagnostics.
“however, are commonly identified through separate MSI analysis and/or additional immunohistochemical staining for mismatch repair enzymes in pathology diagnostics2,3,51.”
From Self-supervised learning reveals clinically relevant histomorphological patterns for therapeutic strategies in colon cancer (2025) · cites this paper as [51]
MSI-high tumors have been linked to a favorable prognosis, characterized by lower differentiation grade, increased T-cell infiltration, and reduced susceptibility to invasiveness and KRAS mutation.
“MSI-high tumors have been linked to a favorable prognosis2,51, characterized by lower differentiation grade, increased T-cell infiltration, and reduced susceptibility to invasiveness and KRAS mutation51”
From Self-supervised learning reveals clinically relevant histomorphological patterns for therapeutic strategies in colon cancer (2025) · cites this paper as [51]
MSI caused by dMMR is detected in approximately 15% of all CRC and in nearly all cases with Lynch syndrome.
“Microsatellite instability (MSI) caused by dysfunctional mismatch repair (dMMR) is detected in approximately 15% of all CRC and in nearly all cases with Lynch syndrome [126].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [126]

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Differential Features of Colorectal Cancers Fulfilling Amsterdam Criteria without Involvement of the Mutator Pathway
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Signatures of mutational processes in human cancer
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MSI-L
Versus, C. C. M.-H., Pawlik, T. M., Raut, R. P., & Rodriguez-bigas, M. A. (2016)

Authors: Boland, C. R., & Goel, A.
Affiliations: Baylor University Medical Center (US)
Corresponding author: Boland, C. Richard
ORCID: Boland, C. Richard
Goel, Ajay
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2010-05
Volume: 138
Issue: 6
Pages: 2073-2087.e3
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2009.12.064
PMC: PMC3037515
OpenAlex: W2094390470
Cited by: 2,456
References: 228
Citations by year: 2026: 140 · 2025: 201 · 2024: 202 · 2023: 191 · 2022: 257 · 2021: 211 · 2020: 194 · 2019: 160 · 2018: 140 · 2017: 115 · 2016: 112 · 2015: 117 · 2014: 111 · 2013: 100 · 2012: 94
FWCI: 11.76
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (R01 CA129286, R01 CA72851)
National Cancer Institute
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
Keywords: microsatellite instability, colorectal cancer, DNA mismatch repair, Lynch syndrome, MLH1 promoter methylation, CpG island methylator phenotype, proximal colon tumors, lymphocyte infiltration, mucinous tumors, signet ring cell carcinoma, prognosis, chemotherapy response
MeSH terms: Animals, Cell Transformation, Neoplastic, Colorectal Neoplasms, Hereditary Nonpolyposis, Humans, Mutation, Phenotype, Risk Factors, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Treatment Outcome, Genetic Predisposition to Disease, Microsatellite Instability, DNA Mismatch Repair

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