ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2008
Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 3 of them syntheses that pooled it.
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Who cites it
150 citing papers in PubMed, 3 syntheses or guidelines pooled it, 227 citations in OpenAlex.
- Prostate radiotherapy and the risk of secondary rectal cancer-a meta-analysis.International journal of colorectal disease · 2022Pooled it
- Pooled it
- MLH1 promoter methylation frequency in colorectal cancer patients and related clinicopathological and molecular features.PloS one · 2013Pooled it
- Prognostic variables in low and high risk stage III colon cancers treated in two adjuvant chemotherapy trials.European journal of cancer (Oxford, England : 1990) · 2021Trial
- Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012Trial
- Deficient mismatch repair system in patients with sporadic advanced colorectal cancer.British journal of cancer · 2009Trial
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 2026Review
- SMAD4 Protein Alterations in Early-Onset Colorectal Cancer: Implications as a Potential Marker for Aggressive Disease and Prognosis-A Clinicopathological and Molecular Analysis of 18 Cases in Patients < 40 Years of Age.Diagnostics (Basel, Switzerland) · 2026Article
- Immune checkpoint blockade in locally advanced rectal cancer with deficient DNA mismatch repair: retrospective multicenter experience.ESMO open · 2026Article
- Deficient mismatch repair/microsatellite instability-high colorectal cancer: current treatment paradigms, limitations and future perspectives.BMJ oncology · 2026Review
- Adjuvant Chemotherapy and Survival in MSI-High Stages II and III Colon Cancer: Impact of Histopathologic Risk Stratification.Annals of surgical oncology · 2025Article
- Traditional and New Views on MSI-H/dMMR Endometrial Cancer.Biomolecules · 2025Review
- Replication-associated mechanisms contribute to an increased CpG > TpG mutation burden in mismatch repair-deficient cancers.Genome medicine · 2025Article
- Molecular Classification of Resected Primary Duodenal Adenocarcinoma.Genes, chromosomes & cancer · 2025Article
- Molecular and functional profiling unravels targetable vulnerabilities in colorectal cancer.Molecular oncology · 2025Article
- A microRNA-regulated transcriptional state defines intratumoral CD8Cell reports · 2025Article
- Predictive Biomarkers and Resistance Mechanisms of Checkpoint Inhibitors in Malignant Solid Tumors.International journal of molecular sciences · 2024Review
- Treatment of Microsatellite-Unstable Rectal Cancer in Sporadic and Hereditary Settings.Clinics in colon and rectal surgery · 2024Review
- Clinical, pathological, and adjuvant chemotherapy use differences among microsatellite unstable and microsatellite stable colon cancers.Journal of the National Cancer Center · 2024Article
- Robust best linear weighted estimator with missing covariates in survival analysis.Statistics in medicine · 2024Article
90 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 9 institutions in 3 countries.
Funding
Abstract
Microsatellite instability (MSI) occurs in 10% to 20% of colorectal cancers (CRC) and has been attributed to both MLH1 promoter hypermethylation and germline mutation in the mismatch repair (MMR) genes. We present results from a large population- and clinic-based study of MLH1 methylation, immunohistochemistry, and MMR germline mutations that enabled us to (a) estimate the prevalence of MMR germline mutations and MLH1 methylation among MSI-H cases and help us understand if all MSI-H CRC is explained by these mechanisms and (b) estimate the associations between MLH1 methylation and sex, age, and tumor location within the colon. MLH1 methylation was measured in 1,061 population-based and 172 clinic-based cases of CRC. Overall, we observed MLH1 methylation in 60% of population-based MSI-H cases and in 13% of clinic-based MSI-H cases. Within the population-based cases with MMR mutation screening and conclusive immunohistochemistry results, we identified a molecular event in MMR in 91% of MSI-H cases: 54% had MLH1 methylation, 14% had a germline mutation in a MMR gene, and 23% had immunohistochemistry evidence for loss of a MMR protein. We observed a striking age difference, with the prevalence of a MMR germline mutation more than 4-fold lower and the prevalence of MLH1 methylation more than 4-fold higher in cases diagnosed after the age of 50 years than in cases diagnosed before that age. We also determined that female sex is an independent predictor of MLH1 methylation within the MSI-H subgroup. These results reinforce the importance of distinguishing between the underlying causes of MSI in studies of etiology and prognosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.