Screening for Lynch syndrome in colorectal cancer: are we doing enough?

Ann Surg Oncol. 2012 Mar;19(3):809-16. doi: 10.1245/s10434-011-2014-7. Epub 2011 Aug 31.


Purpose: The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.

Methods: A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.

Results: A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (n = 64) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of MSH2 on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.

Conclusions: Strict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients.

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / surgery
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • DNA Methylation
  • DNA-Binding Proteins
  • Female
  • Genetic Testing*
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • Male
  • Microsatellite Instability
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / analysis*
  • Nuclear Proteins / analysis
  • Promoter Regions, Genetic
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein