Familial Cancer

, Volume 16, Issue 3, pp 351–355 | Cite as

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

  • Mohammad R. Akbari
  • Shiyu Zhang
  • Deborah Cragun
  • Ji-Hyun Lee
  • Domenico Coppola
  • John McLaughlin
  • Harvey A. Risch
  • Barry Rosen
  • Patricia Shaw
  • Thomas A. Sellers
  • Joellen Schildkraut
  • Steven A. NarodEmail author
  • Tuya Pal
Original Article


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.


Ovarian cancer Microsatellite Instability 



Financial Support: Supported by grants R01 CA111914 (TP), K07 CA108987 (TP), R01 CA063682 (HAR), R01 CA063678 (SN) and R01 CA080978 (SN) from the National Cancer Institute.

Compliance with ethical standards

Conflict of interest

The author’s declare no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Mohammad R. Akbari
    • 1
  • Shiyu Zhang
    • 1
  • Deborah Cragun
    • 2
  • Ji-Hyun Lee
    • 2
  • Domenico Coppola
    • 2
  • John McLaughlin
    • 3
  • Harvey A. Risch
    • 4
  • Barry Rosen
    • 5
    • 6
  • Patricia Shaw
    • 7
  • Thomas A. Sellers
    • 2
  • Joellen Schildkraut
    • 8
  • Steven A. Narod
    • 1
    Email author
  • Tuya Pal
    • 2
  1. 1.Women’s College Research Institute, Women’s College HospitalUniversity of TorontoTorontoCanada
  2. 2.Departments of Cancer Epidemiology, Moffitt Cancer CenterBiostatistics, Anatomic Pathology, and Experimental TherapeuticsTampaUSA
  3. 3.Samuel Lunenfeld Research Institute, and Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada
  4. 4.Department of Chronic Disease EpidemiologyYale School of Public HealthNew HavenUSA
  5. 5.Department of Gynecology-Oncology, Princess Margaret HospitalUniversity of TorontoTorontoCanada
  6. 6.Department of Obstetrics and Gynecology, Faculty of MedicineUniversity of TorontoTorontoCanada
  7. 7.Department of PathologyPrincess Margaret HospitalTorontoCanada
  8. 8.Department of Community and Family Medicine, Duke Comprehensive Cancer CenterDuke University Medical CenterDurhamUSA

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