Analysis of Lynch Syndrome Mismatch Repair Genes in Women with Endometrial Cancer

Oncology. 2016;91(3):171-6. doi: 10.1159/000447972. Epub 2016 Jul 12.

Abstract

Objective: Endometrial cancer is the second most frequent neoplasm in women with Lynch syndrome (LS). We sought to assess whether analyzing women with endometrial cancer would identify families with LS not identified with current clinical criteria.

Methods: We included women diagnosed with endometrial cancer younger than 50 years and also older if they had a family cancer history associated with LS. In blood samples obtained, we analyzed mutations in mismatch repair (MMR) genes, as well as protein expression by immunohistochemistry and microsatellite instability (MSI) in tumour tissue.

Results: A total of 103 patients were enrolled. We detected 14 pathogenic mutations and 4 genetic variants of unknown clinical significance in MMR genes. We found MSI in 41.66% of the women with a pathogenic mutation. In this group, 76.92% showed loss of at least one MMR protein. Women with mutations were younger at diagnosis, but all of them had a family history compatible with LS.

Conclusions: Analysis of the MMR genes, in particular MSH6, seems to be appropriate in women with endometrial cancer and a family history of tumours associated with LS.

MeSH terms

  • Adult
  • Age Factors
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mismatch Repair / genetics*
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • Endometrial Neoplasms / chemistry
  • Endometrial Neoplasms / genetics*
  • Female
  • Humans
  • Microsatellite Instability*
  • Middle Aged
  • MutL Protein Homolog 1 / analysis
  • MutL Protein Homolog 1 / genetics
  • MutS Homolog 2 Protein / analysis
  • MutS Homolog 2 Protein / genetics
  • Mutation
  • Prospective Studies
  • Retrospective Studies

Substances

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