Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions

ANZ J Surg. 2017 Dec;87(12):1006-1010. doi: 10.1111/ans.13483. Epub 2016 Mar 16.

Abstract

Background: Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing.

Methods: Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry.

Results: There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC.

Conclusion: Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance.

Keywords: HNPCC; Lynch syndrome; inherited colorectal cancer.

MeSH terms

  • Adult
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • DNA Mismatch Repair / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Humans
  • Male
  • Medical History Taking / methods*
  • Microsatellite Instability
  • MutL Protein Homolog 1 / genetics
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics

Substances

  • MLH1 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MutL Protein Homolog 1