Correlation between germline mutations in MMR genes and microsatellite instability in ovarian cancer specimens

Fam Cancer. 2017 Jul;16(3):351-355. doi: 10.1007/s10689-017-9973-1.


A high proportion of ovarian cancers from women who carry germline mutations in mismatch repair (MMR) genes demonstrate microsatellite instability (MSI). The utility of pre-screening ovarian cancer specimens for MSI to identify potential patients for germline screening for MMR mutations is uncertain. 656 women with malignant ovarian cancer underwent both MSI testing and germline mutation testing for large rearrangements in three MMR genes, MLH1, MSH2 and MSH6. Germline DNA sequencing data for the same genes was available. Among the 656 women, only four (0.6%) carried a clearly pathogenic MMR mutation. All four cancers from patients with mutations had loss of two or more microsatellite markers (MSI-high). Eighty-four of 652 (13.0%) women without a mutation had MSI-high ovarian cancers. Using MSI-high as a prescreening criterion, the sensitivity of MSI testing to identify germline MMR gene mutations was 100% and the positive predictive value was 4.5%. Germline mutations in MLH1, MSH2 and MSH6 are rare among unselected cases of ovarian cancer. Patients with germline mutations often will have MSI-positive cancers and pre-screening of ovarian cancer specimens may be an efficient way of identifying patients with Lynch syndrome.

Keywords: Microsatellite Instability; Ovarian cancer.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Ovarian Epithelial
  • DNA Mismatch Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Germ-Line Mutation
  • Humans
  • Microsatellite Instability
  • Middle Aged
  • MutL Protein Homolog 1 / genetics*
  • MutS Homolog 2 Protein / genetics*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Ovarian Neoplasms / genetics*
  • Sensitivity and Specificity


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