Current clinical topics of Lynch syndrome

Int J Clin Oncol. 2019 Sep;24(9):1013-1019. doi: 10.1007/s10147-018-1282-7. Epub 2018 May 9.


Lynch syndrome (LS) is one of the most common genetic cancer syndromes, occurring at a rate of 1 per 250-1000 in the general population. This autosomal dominant disease is caused by a germline variant in one of the four mismatch repair genes, MSH2, MLH1, MSH6, PMS2, or the EPCAM gene. LS develops at early ages in colorectal cancer (CRC), endometrial cancer, and various other associated tumors. Accurate diagnosis of LS and utilization of various risk-reduction strategies such as surveillance, prophylactic surgery, and chemoprevention could improve clinical outcomes. The efficacy of surveillance has only been proven for CRC; however, specialists have proposed surveillance for other LS associated tumors. Universal screening for tumor tissue using microsatellite instability testing or the mismatch repair protein immunochemistry in all CRC or endometrial cancers is recommended not only as a diagnostic tool for LS, but also as a predictive, prognostic, and therapeutic marker. Next-generation sequencing methods have revealed several conditions with phenotypes similar to LS, such as Lynch-like syndrome, constitutional mismatch repair deficiency syndrome, and polymerase proofreading-associated polyposis. Distinguishing LS from these similar conditions is clinically important, since clinical management for patients differs according to the conditions. Recently, immune checkpoint inhibitors have been shown to be a promising treatment against mismatch repair-deficient (dMMR) solid tumors. The efficacy of immune-checkpoint inhibitors in LS-associated tumors has been shown to be similar to that in sporadic dMMR tumors. This review discusses current clinical topics related to LS screening, diagnosis, surveillance, and therapy.

Keywords: Immune-checkpoint inhibitors; Lynch syndrome; Mismatch repair; Multi gene panel testing; Universal screening.

Publication types

  • Review

MeSH terms

  • Anticarcinogenic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / therapy*
  • DNA Mismatch Repair / genetics
  • Endometrial Neoplasms / surgery
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Immunohistochemistry
  • Ovarian Neoplasms / surgery
  • Risk Reduction Behavior


  • Anticarcinogenic Agents
  • Biomarkers, Tumor