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5 Understanding the clinical implication of mismatch repair deficiency in endometrioid endometrial cancer through a prospective study
  1. S Kim1,
  2. A Tone2,
  3. A Pollett3,
  4. R Kim4,
  5. M Cesari3,
  6. B Clarke3,
  7. L Eiriksson5,
  8. T Hart6,
  9. S Holter7,
  10. A Lytwyn8,
  11. M Maganti9,
  12. L Oldfield10,
  13. T Pugh10,
  14. S Gallinger11,
  15. M Bernardini1,
  16. A Oza12,
  17. V Dube3,
  18. J Lerner-Ellis3,
  19. E Van de Laar2,
  20. D Vicus2 and
  21. S Ferguson1
  1. 1Department of Obstetrics and Gynaecology, 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. 4Fred A Litwin Family Centre for Genetic Medicine, University Health Network, Canada
  5. 5Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Juravinski Cancer Centre, McMaster University, Canada
  6. 6Department of Psychology, Ryerson University, Canada
  7. 7Zane Cohen Centre for Digestive Diseases, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Canada
  8. 8Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Canada
  9. 9Department of Biostatistics, Princess Margaret Cancer Centre/University Health Network, University of Toronto, Canada
  10. 10Department of Medical Biophysics, University of Toronto, Canada
  11. 11Division of General Surgery, Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Canada
  12. 12Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Canada


Objectives Findings on impact of mismatch repair deficiency (MMRd) on patient outcomes in endometrial cancer (EC) have been inconsistent to date. The objective of this study was to compare oncologic outcomes between MMRd and MMR-intact (MMRi) endometrioid EC (EEC).

Methods Between 2015–2018, we prospectively recruited 668 EC cases from three cancer centers in Ontario, Canada. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinicopathological, treatment and survival data were compared between MMRd and MMRi cases.

Results Out of 668, there were 496 EEC (74%), with 347 MMRi (70%) and 149 MMRd (30%) cases treated with surgery and with complete follow-up information. Median follow-up was 16.8 months (6–96 months). MMRd tumors tended to be grade 2 or 3 (56% vs. 29%, p<0.001), with propensity for lymphovascular space invasion (LVSI) (29% vs. 17%, p=0.004) and received more adjuvant treatment (45% vs. 33%, p=0.03). This group also had significantly lower 3-year RFS (78% vs. 89%, p=0.02) although there was no difference in OS (p=0.91). MLH1/PMS2 deficient tumors had the lowest 3-year RFS compared to intact and other MMRd tumors (76% vs. 89% vs 87%, p=0.02). After adjusting for age, stage, grade, use of adjuvant treatment, and LVSI status, MLH1/PMS2 deficiency was still associated with the lowest RFS (p=0.05).

Abstract 5 Figure 1

Comparison of recurrence free survival between mismatch repair deficient (MMRd) and mismatch repair intact (MMRi) endometrioid endometrial cancers

Conclusions MLH1/PMS2 deficient EECs exhibit more aggressive features compared to other MMRd and MMRi cases, with worse RFS. This may indicate an inherent difference in tumor biology, suggesting the importance of individualized management based on tumor’s molecular phenotype.

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