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Tumor site discordance in mismatch repair deficiency in synchronous endometrial and ovarian cancers
  1. Soyoun Rachel Kim1,2,
  2. Alicia Tone1,
  3. Raymond Kim3,4,5,
  4. Matthew Cesari6,
  5. Blaise Clarke6,
  6. Lua Eiriksson7,
  7. Tae Hart4,8,
  8. Melyssa Aronson4,
  9. Spring Holter4,
  10. Alice Lytwyn9,
  11. Manjula Maganti10,
  12. Leslie Oldfield11,
  13. Steven Gallinger12,
  14. Marcus Q Bernardini1,2,
  15. Amit M Oza5,
  16. Bojana Djordjevic6,13,
  17. Jordan Lerner-Ellis6,
  18. Emily Van de Laar1,
  19. Danielle Vicus1,2,13,
  20. Trevor J Pugh11,14,
  21. Aaron Pollett6,15 and
  22. Sarah Elizabeth Ferguson1,2
  1. 1 Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  2. 2 Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
  3. 3 Fred A Litwin Family Centre for Genetic Medicine, University Health Network, Toronto, Ontario, Canada
  4. 4 Zane Cohen Centre for Digestive Diseases, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Toronto, Ontario, Canada
  5. 5 Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  6. 6 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
  7. 7 Gynecologic Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada
  8. 8 Psychology, Ryerson University, Toronto, Ontario, Canada
  9. 9 Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  10. 10 Biostatistics, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  11. 11 Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  12. 12 General Surgery, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  13. 13 Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  14. 14 Ontario Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada
  15. 15 Pathology and Laboratory Medicine, Mount Sinai Hospital Pathology and Laboratory Medicine, Toronto, Ontario, Canada
  1. Correspondence to Dr Sarah Elizabeth Ferguson, Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2C1, Canada; sarah.ferguson{at}


Objectives For synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests.

Methods 30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing.

Results Of 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a PMS2 pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium.

Conclusions There was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.

  • lynch syndrome II
  • uterine cancer
  • ovarian cancer

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  • Contributors SRK: data curation, formal analysis, project administration, visualization, writing—original draft, and writing—review and editing. AT: conceptualization, data curation, investigation, methodology, and writing—review and editing. RK, MC, BC, AL, JL-E, and AP: investigation and writing—review and editing. LE, DV: investigation, resources, and writing—review and editing. TH, MA, and SH: resources and writing—review and editing. MM and LO: formal analysis and writing—review and editing. SG, MQB, and AMO: conceptualization and writing—review and editing, BD: writing—review and editing. EV: data curation, project administration, and writing—review and editing. TJP: formal analysis, investigation, and writing—review and editing. SEF: conceptualization, formal analysis, funding acquisition, project administration, investigation, methodology, supervision, and writing—review and editing.

  • Funding We have received funding from the Canadian Cancer Society (grant No 704038).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Institutional research ethics board approval was obtained from all three study sites.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.