ArticleHuman pathology2020
Unexpected expression of mismatch repair protein is more commonly seen with pathogenic missense than with other mutations in Lynch syndrome.
Article in Human pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- EMQN best practice guidelines for analysis and reporting of microsatellite instability in solid tumours.European journal of human genetics : EJHG · 2026Guideline
- Characterisation of a Portuguese origin founder missense variant in MSH6.European journal of human genetics : EJHG · 2026Article
- Genetic Landscape of Lynch Syndrome in a High-Risk Serbian Cohort: Predominance ofInternational journal of molecular sciences · 2026Article
- Phenotypic heterogeneity in carriers of a pathogenic MSH2 variant: implications for the diagnosis of Lynch syndrome.Journal of cancer research and clinical oncology · 2026Article
- Current Status of the Diagnosis and Treatment of Mismatch Repair Deficient Colorectal Cancer.Biomedicines · 2026Review
- Bayesian Integration of Tumor Mutational Signatures and Somatic Features Refines Pathogenicity Assessment of Germline Mismatch Repair Variants.Human mutation · 2026Article
- Lights and shadows of microsatellite status characterization in gastrointestinal cancers in the era of cancer precision therapy.Pathologica · 2025Review
- Novel microsatellite instability test of sebaceous tumours to facilitate low-cost universal screening for Lynch syndrome.Clinical and experimental dermatology · 2025Article
- Advances in diagnostic and therapeutic applications of mismatch repair loss in cancer.DNA repair · 2025Review
- MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma.Acta neuropathologica · 2025Article
- MSIsensor-RNA: Microsatellite Instability Detection for Bulk and Single-cell Gene Expression Data.Genomics, proteomics & bioinformatics · 2024Article
- Review
- Testing region selection and prognostic analysis ofGastroenterology report · 2024Article
- A novel colorectal cancer test combining microsatellite instability andBJC reports · 2024Article
- Tumor-independent Detection of Inherited Mismatch Repair Deficiency for the Diagnosis of Lynch Syndrome with High Specificity and Sensitivity.Cancer research communications · 2023Article
- Mismatch repair deficiency testing in Lynch syndrome-associated urothelial tumors.Frontiers in oncology · 2023Article
- Reply to Singh et al.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- Prospective Statewide Study of Universal Screening for Hereditary Colorectal Cancer: The Ohio Colorectal Cancer Prevention Initiative.JCO precision oncology · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
It has been observed that some patients with colorectal cancer due to germline or double somatic pathogenic variants in the mismatch repair (MMR) genes may have intact protein expression in their tumors as assessed by immunohistochemistry (IHC). This has been speculated to occur more frequently in Lynch syndrome (LS) cases due to pathogenic missense mutations, leading to expression of a full-length but nonfunctional protein with retained antigenicity. Our goals were to study the frequency of unexpected MMR expression in colorectal cancers among LS cases with missense mutations, LS cases with truncating mutations, as well as cases with double somatic MMR mutations and evaluate if the unexpected MMR expression is more common in certain categories. IHC slides were available for 82 patients with MMR deficiency without methylation, which included 56 LS cases and 26 double somatic MMR mutation cases. Sixteen of 82 MMR-defective cases showed unexpected MMR expression, with 10 cases showing tumor staining weaker than the control and 6 cases (7%) showing intact staining. Unexpected MMR expression was most commonly seen with LS cases with missense mutations (4 of 9, 44%), followed by MMR double somatic mutation cases (7 of 26, 27%), and finally by LS cases with truncating mutations (5 of 47, 11%). Cautious interpretation of MMR IHC is advised when dealing with tumor staining that is weaker than the control regardless of the percentage of tumor staining as these cases may harbor pathogenic MMR gene mutations. Missense mutations may account for some LS cases that may be missed by IHC alone. Strict adherence to proper interpretation of IHC with attention to staining intensity and the status of heterodimer partner protein will prevent many potential misses.
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