{"entity":{"id":"paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009","kind":"paper","name":"Deficient mismatch repair system in patients with sporadic advanced colorectal cancer","aka":[],"tldr":"Broken DNA repair is common in bowel cancers removed by surgery but rare once the disease has spread, which is evidence that those tumours are less able to metastasise in the first place.","summary":"Data were collected from a phase 3 study in 820 patients with advanced colorectal cancer. Mismatch repair protein expression was examined by immunohistochemistry, with microsatellite instability analysis and MLH1 promoter methylation status. Deficient mismatch repair was found in only 18 of 515 evaluable patients (3.5%), 13 of them caused by MLH1 promoter hypermethylation. Median overall survival was 17.9 months in proficient patients, 7.4 months in those deficient through MLH1 hypermethylation and 10.2 months in all deficient patients; disease control was 83% against 56%. The authors concluded that deficient mismatch repair is rare in sporadic advanced colorectal cancer, supporting the hypothesis that such tumours have reduced metastatic potential.","asOf":"2026-09-24","links":[{"label":"Koopman et al., Br J Cancer 2009: deficient mismatch repair in 515 patients with sporadic advanced colorectal cancer","url":"https://doi.org/10.1038/sj.bjc.6604867"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19165197/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["msi-mmr-testing","histopathology-ihc"],"targets":["mmr","mlh1"],"drugs":[],"companies":[],"institutions":["radboudumc"],"pathways":["mismatch-repair-msi"],"terms":["msi","mss-pmmr","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2009,"doi":"10.1038/sj.bjc.6604867","pmid":"19165197","authors":"Koopman M, Kortman GA, Mekenkamp L, et al.","paperType":"observational","findings":["Deficient mismatch repair in 18 of 515 evaluable advanced patients (3.5%), 13 from MLH1 hypermethylation.","Median overall survival 17.9 months proficient against 10.2 months deficient."],"whatItMeans":"It is the reason the immunotherapy-eligible fraction of metastatic colorectal cancer is about 5% rather than the 15% quoted for resected disease, and it frames microsatellite instability as a barrier to metastasis that becomes a liability once crossed.","caveats":["Small number of deficient patients, so the survival comparison is imprecise.","Predates checkpoint inhibitors, so the prognosis described no longer applies to treated patients."],"changedPractice":false,"participants":820},"route":"/key-papers/paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"}],"target":[{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"mlh1","kind":"target","name":"MLH1","route":"/targets/mlh1/"}],"institution":[{"id":"radboudumc","kind":"institution","name":"Radboudumc Centre for Oncology","route":"/institutions/radboudumc/"}],"pathway":[{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","route":"/terms/mss-pmmr/"}],"journal":[{"id":"british-journal-of-cancer","kind":"journal","name":"British Journal of Cancer","route":"/journals/british-journal-of-cancer/"}]}}