A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory

J Cell Mol Med. 2010 Jan;14(1-2):181-97. doi: 10.1111/j.1582-4934.2009.00977.x. Epub 2009 Nov 19.


Lynch syndrome (LS) is caused by mutations in mismatch repair genes and is characterized by a high cumulative risk for the development of mainly colorectal carcinoma and endometrial carcinoma. Early detection of LS is important since surveillance can reduce morbidity and mortality. However, the diagnosis of LS is complicated by the absence of a pre-morbid phenotype and germline mutation analysis is expensive and time consuming. Therefore it is standard practice to precede germline mutation analysis by a molecular diagnostic work-up of tumours, guided by clinical and pathological criteria, to select patients for germline mutation analysis. In this review we address these molecular analyses, the central role for the pathologist in the selection of patients for germline diagnostics of LS, as well as the molecular basis of LS.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / physiopathology
  • DNA Mismatch Repair / genetics*
  • DNA Mutational Analysis
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Germ-Line Mutation
  • Humans
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics
  • Nuclear Proteins / genetics
  • Pathology, Molecular
  • Proto-Oncogene Proteins B-raf / genetics
  • Risk Factors


  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein