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4 Refining pathologic interpretation of endometrial carcinomas: lessons learned from a nationwide study in a new era of molecular classification
  1. E Thompson1,
  2. J Huvila1,
  3. S Leung2,
  4. J Irving3,
  5. N van der Westhuizen3,
  6. M Kinloch4,
  7. A Lytwyn5,
  8. M Sur5,
  9. C Parra-Herran6,
  10. A Yasmeen7,
  11. F Gougeon8,
  12. C Morin9,
  13. K Grondin9,
  14. S Offman10,
  15. T Salisbury11,
  16. E He12,
  17. J Lawson12,
  18. J Vanden Broek13,
  19. C Bell14,
  20. K Ennour-Idrissi9,
  21. C Wohlmuth15,
  22. D Vicus16,
  23. D Vicus16,
  24. W Gotlieb17,
  25. L Helpman18,
  26. A Lum1,
  27. J Senz1,
  28. D Huntsman1,
  29. B Gilks11 and
  30. JN McAlpine19
  1. 1Molecular Oncology, University of British Columbia, Canada
  2. 2Genetic Pathology Evaluation Centre, University of British Columbia, Canada
  3. 3Pathology and Laboratory Medicine, Royal Jubilee Hospital and the University of British Columbia, Canada
  4. 4Pathology and Laboratory Medicine, University of Saskatchewan, Canada
  5. 5Pathology and Molecular Medicine, McMaster University, Canada
  6. 6Laboratory Medicine and Pathobiology, University of Toronto and Sunnybrook Health Sciences Centre, Canada
  7. 7Gynecologic Oncology, Segal Cancer Center, Jewish General Hospital, McGill University, Canada
  8. 8Department of Pathology, University of Montreal, Canada
  9. 9Pathology Department, Centre Hospitalier Universitaire de Québec, L’Hôtel-Dieu de Québec, Laval University, Canada
  10. 10Anatomical Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Canada
  11. 11Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Canada
  12. 12MD Undergraduate Program, University of British Columbia, Canada
  13. 13Faculty of Science, University of British Columbia, Canada
  14. 14College of Medicine, University of Saskatchewan, Canada
  15. 15Gynecologic Oncology, Department of Surgical Oncology, University Health Network, Canada
  16. 16Gynecologic Oncology, Centre Hospitalier Universitaire de Québec, L’Hôtel-Dieu de Québec, Canada
  17. 17Gynecologic Oncology, Jewish General Hospital, McGill University, Canada
  18. 18Gynecologic Oncology, Juravinski Cancer Center and McMaster University, Canada
  19. 19Gynecologic Oncology, Vancouver General Hospital and the University of British Columbia, Canada


Objectives Molecular classification of endometrial carcinoma (EC) enables consistent classification of tumours and provides valuable prognostic and predictive information. Herein we describe molecular subtype distribution and histomorphologic correlates in recently diagnosed (2016) ECs from across Canada.

Methods Molecular classification was performed on representative tumour specimens from participating centres. Clinicopathologic, management and outcome data were collected (REDCap).

Results 1453 ECs from 30 centres have been identified. Complete molecular (ProMisE) and outcome data is reportable for 862 patients. Histologic and clinicopathologic parameters associated with molecular subtype and are summarised in table 1. Amongst participating centres, routine testing of MMR and p53 immunohistochemistry (IHC) was performed in only 23.5% (range 3.5–80.0% per centre) and 15% (2.2–45.7%) of cases respectively. We found p53 abn ECs across a range of histotypes, including low grade endometrioid EC. Subclonal p53 staining was observed in 3.9% of cases and significantly associated with the presence of pathogenic POLE mutations (p≤0.001). Subclonal MMR IHC expression was seen in 3.5% of cases and has previously been shown to occur predominantly in the context of MLH1 hypermethylation. MMRd was significantly associated with LVI (p <0.001). ProMisE subtype was significantly associated with clinical outcomes (p<0.001) even in low stage disease [OS p=0.045, DSS p=0.009, PFS p=0.005 for stage I].

Abstract 4 Table 1

Univariable association of clinicopathologic characteristics by proactive molecular risk classifier for endometrial cancer (ProMisE) subtype

Conclusions Observation of unusual or unexpected p53 and MMR IHC staining patterns and associated clinical implications highlight the importance of routine testing of these parameters in ECs.

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