Microsatellite instability screening in colorectal adenomas to detect Lynch syndrome patients? A systematic review and meta-analysis

Eur J Hum Genet. 2020 Mar;28(3):277-286. doi: 10.1038/s41431-019-0538-7. Epub 2019 Nov 6.


The colorectal cancer spectrum has changed due to population screening programs, with a shift toward adenomas and early cancers. Whether it would be a feasible option to test these adenomas for detection of Lynch syndrome (LS) patients is unclear. Through meta-analysis and systematic review, risk factors for DNA mismatch repair deficiency (dMMR) and microsatellite instability (MSI) in adenomas were identified in LS and unselected patient cohorts. Data were extracted for patient age and MMR variant together with adenoma type, grade, size, and location. A total of 41 studies were included, and contained more than 519 LS patients and 1698 unselected patients with 1142 and 2213 adenomas respectively. dMMR/MSI was present in 69.5% of conventional adenomas in LS patients, compared with 2.8% in unselected patients. In the LS cohort, dMMR/MSI was more frequently present in patients older than 60 years (82% versus 54%). dMMR/MSI was also more common in villous adenomas (84%), adenomas over 1 cm (81%), and adenomas with high grade dysplasia (88%). No significant differences were observed for dMMR/MSI in relation to MMR variants and location of adenomas. In the context of screening, we conclude that detection of dMMR/MSI in conventional adenomas of unselected patients is uncommon and might be considered as indication for LS testing. Within the LS cohort, 69.5% of LS patients could have been detected through dMMR/MSI screening of their conventional adenomas.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adenoma / diagnosis
  • Adenoma / genetics*
  • Adult
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Female
  • Humans
  • Male
  • Microsatellite Instability*
  • Middle Aged


  • Biomarkers, Tumor