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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.
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.
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.
Shares Radboudumc Centre for Oncology, Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).
Shares MLH1, MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability.
Shares MLH1, MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability.
Shares MLH1, MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Immunohistochemistry (IHC), Histopathology & immunohistochemistry, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares British Journal of Cancer, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Radboudumc Centre for Oncology, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability, Colorectal cancer.
Shares MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).