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340 Performance characteristics of screening strategies to identify Lynch syndrome in women with non-serous and non-mucinous ovarian cancer
  1. S Kim1,
  2. A Tone2,
  3. A Pollett3,
  4. M Cesari3,
  5. B Clarke3,
  6. L Eiriksson4,
  7. T Hart5,
  8. S Holter6,
  9. A Lytwyn7,
  10. M Maganti8,
  11. L Oldfield9,
  12. T Pugh9,
  13. S Gallinger10,
  14. M Bernardini1,
  15. A Oza11,
  16. D Vicus12,
  17. V Dube13,
  18. R Kim14 and
  19. S Ferguson1
  1. 1Department of Obstetrics and Gynecology, University of Toronto, Canada
  2. 2Division of Gynecologic Oncology, Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Canada
  3. 3Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada
  4. 4Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Juravinski Cancer Centre, McMaster University, Canada
  5. 5Department of Psychology, Ryerson University, Canada
  6. 6Zane Cohen Centre for Digestive Diseases, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Canada
  7. 7Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Canada
  8. 8Department of Biostatistics, Princess Margaret Cancer Centre/University Health Network, University of Toronto, Canada
  9. 9Department of Medical Biophysics, University of Toronto, Canada
  10. 10Division of General Surgery, Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Canada
  11. 11Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Canada
  12. 12Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Centre, University of Toronto, Canada
  13. 13Trillium Health Partners/Credit Valley Hospital, Canada
  14. 14Fred A Litwin Family Centre for Genetic Medicine, University Health Network, Canada


Objectives The incidence of Lynch syndrome (LS) and the optimal screening strategy has not been determined for women with ovarian cancer (OC). We compared the performance characteristics between immunohistochemistry (IHC) for mismatch repair (MMR) proteins, microsatellite instability (MSI) testing and family history.

Methods Women with non-serous/mucinous OC were prospectively recruited from three cancer centers in Ontario, Canada. Tumors were assessed for defects in MMR by IHC and MSI testing. All women completed a family history assessment and underwent germline testing for LS. The performance characteristics were compared between the screening strategies compared to germline result.

Results Of 215 women, 185 had OC alone (86%) and 30 had synchronous OC and endometrial cancers (14%). Germline data was available for 189 women (88%). Twenty-eight were MMR deficient (MMRd) by IHC (13%; N = 215), one (0.5%) IHC equivocal and 19 (12%; N=162) were MSI-high (MSI-H). Of those with MMRd, 11 had germline mutation (39%; N=28). In total, thirteen women (7%; N = 189) had germline mutations: 3 MLH1, 7 MSH6, 1 MSH2 and 2 PMS2. Combined IHC and MSI testing after excluding MLH1 hypermethylated cases was the best screening strategy with sensitivity of 92.3%, specificity of 97.7%, PPV of 75% and NPV of 99.4%. Family history had the lowest performance characteristics with sensitivity of 55%.

Abstract 340 Table 1

Performance characteristics of screening strategies for identifying mismatch repair germline mutations (Lynch syndrome) in women with newly diagnosed non-serous/non-mucinous ovarian cancer. *Indicates calculation excluding MLH1 hypermethylated cases. Abbreviations: IHC, immunohistochemistry; MSI, microsatellite instability; eFHQ, extended family history questionnaire; PPV, positive predictive value; NPV, negative predictive value

Conclusions The most superior screening strategy to identify women with LS in this population is combined IHC and MSI testing after MLH1 hypermethylation testing and should be considered as standard of care.

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