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382 Molecular classification of endometrial carcinoma substantially changing risk-assessment: Results from a european multicentre initiative
  1. S Kommoss1,
  2. M Grube1,
  3. K Knoll2,
  4. A Lum3,
  5. C Brambs4,
  6. N Pauly5,
  7. F Kommoss6,
  8. S Heublein7,
  9. M Battista8,
  10. S Mittelstadt1,
  11. A Rohner1,
  12. T Preaetorius1,
  13. A Hasenburg9,
  14. B Ataseven5;10,
  15. A Talhouk11,
  16. J Diebold12,
  17. AG Zeimet2,
  18. A Staebler13 and
  19. J Mcalpine11
  1. 1Tübingen University Hospital, Department of Women’s Health, Germany
  2. 2Innsbruck Medical University, Department Gynecology and Obstetrics, Austria
  3. 3BC Cancer Research Centre, Molecular Oncology, Vancouver, Canada
  4. 4Lucerne Cantonal Hospital, Department Gynecology and Obstetrics, Lucerne, Switzerland
  5. 5Kliniken Essen Mitte (KEM), Department of Gynecology and Gynecologic Oncology, Germany
  6. 6Heidelberg University Hospital, Institute of Pathology, Germany
  7. 7Heidelberg University Hospital, Department Gynecology and Obstetrics, Heidelberg, Germany
  8. 8University Medical Centre of the Johannes Gutenberg University Mainz, Department of Gynaecology and Obstetrics
  9. 9, Mainz University Hospital, Department Gynecology and Obstetrics
  10. 10Frauenklinik in der Maistraße, München, Germany
  11. 11University of British Columbia and British Columbia Cancer Agency, Division of Gynecologic Oncology, Canada
  12. 12Lucerne Cantonal Hospital, Institute of Pathology, Lucerne, Switzerland
  13. 13Tübingen University Hospital, Institute of Pathology and Neuropathology, Germany


Introduction/Background*Endometrial carcinoma patient care was based on histopathologic examination for many years. However, conventional pathologic features are known to suffer from high inter-observer variability and may be irreproducible in many cases. TCGA-derived molecular classification was shown to provide clinically meaningful data and was recently introduced to ESGO/ESTRO/ESP endometrial carcinoma consensus guidelines. It was the aim of this study to quantify alterations in risk-assessment if molecular classification is added to conventional prognosticators.

Methodology Consecutive primary endometrial carcinoma patients diagnosed in 2016 were identified in participating centres. Original risk classification (‘ORC16’, ESGO/ESMO guidelines 2016) was compared to current molecular-based risk assessment (‘MBR21’, ESGO/ESMO guidelines 2021). Clinical and histopathological data were collected and tumor specimens were retrospectively submitted to PMS2, MSH6 and p53 immunohistochemistry and POLE mutation testing.

Result(s)*226 patients were identified across five major European gynecologic oncology centres. Complete molecular and clinical data were available from 198 cases with a median follow-up time of 52.1 months. Median age was 64.9 years (30.9-90.9), 165 cases (83,3%) were endometrioid histotype. Grade distribution included 85(42.9%) G1, 63(31.8%) G2, and 46(23.3%) G3 tumors. 98(49.5%) patients had stage IA disease, with the remaining stage IB (n=51;25.8%), stage II (n=16;8.0%), and stage III/IV (n=33;16.7%). Molecular classification yielded 43(21.7%) MMR-D, 18(9.1%) POLE, 43(21.7%) p53abn, and 94(47.5%) p53wt tumors. If ORC16 was compared to MBR21, risk was found to be higher in 15(7.6%) cases, whereas 27(13.6%) cases were assigned to a lower risk group. No survival events were observed in the 9 patients where risk was changed from high-intermediate or high to low-risk.

Conclusion*We were able to demonstrate clinically relevant alterations of endometrial carcinoma risk assessment in a significant number of patients after adding TCGA-derived molecular data to conventional risk classification. Potential molecular-guided changes in patient management may help to avoid over- and undertreatment and will ultimately give rise to precision medicine strategies in endometrial carcinoma patient care.

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