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28 Prevalence and prognosis of lynch syndrome and sporadic mismatch repair deficiency in the combined PORTEC-1,-2 and -3 endometrial cancer trials
  1. C Post1,
  2. E Stelloo1,
  3. V Smit1,
  4. D Ruano1,
  5. CM Tops1,
  6. L Vermij1,
  7. TA Rutten1,
  8. IM Jürgenliemk-Schulz2,
  9. LC Lutgens3,
  10. JJ Jobsen4,
  11. RA Nout1,
  12. EJ Crosbie5,
  13. ME Powell6,
  14. L Mileshkin7,
  15. A Leary8,
  16. P Bessette9,
  17. SM de Boer1,
  18. N Horeweg1,
  19. T van Wezel1,
  20. T Bosse1 and
  21. CL Creutzberg1
  1. 1Leiden University Medical Center, Netherlands
  2. 2University Medical Center Utrecht, Netherlands
  3. 3MAASTRO Clinic, Netherlands
  4. 4Medical Spectrum Twente, Netherlands
  5. 5University of Manchester, St Mary’s Hospital, UK
  6. 6Barts Health NHS Trust, UK
  7. 7Peter MacCallum Cancer Centre, Australia
  8. 8Gustave Roussy Cancer Center – INSERM U981, Université Paris Saclay, France
  9. 9University of Sherbrooke, Canada


Introduction Here we aimed to evaluate the prevalence and prognosis of Lynch Syndrome (LS)-associated endometrial cancer (EC) in relation to sporadic mismatch repair deficient EC (MMRd-EC) in the combined PORTEC-1,-2 and 3 trials comprising 1336 ECs.

Methods MMR-status was determined by MMR-immunohistochemistry (MLH1/PMS2/MSH6/MSH2). MMRd-ECs with detected promoter hypermethylation of MLH1 were classified as sporadic (methylated MMRd-EC). For unmethylated MMRd-EC cases tumor and normal tissue next-generation sequencing was performed. ECs with MMR germline mutations were classified as LS-associated (LS MMRd-EC). Unmethylated MMRd-ECs without MMR germline mutations were classified as MMRd-EC due to other causes (other MMRd-EC). Overall and recurrence-free survival were estimated and compared using Kaplan-Meier method and pairwise log-rank test.

Results Among the 1336 ECs, 926 were MMR proficient. Of the 410 MMRd-EC, 376 could be fully triaged; 281 (75%) were methylated MMRd-ECs; 37 (10%) LS MMRd-ECs, and 58 (15%) other MMRd-ECs. The overall LS prevalence was 2.8%. Overall 5-year survival for LS MMRd-EC was 89% (95%CI 79–100%; p=0.055), other MMRd-EC 96% (92–100%; p=0.001), both compared to methylated MMRd-EC 79% (74–84%); 5-year recurrence-free survival was 92% (84–100%; p=0.123), 95% (89–100%; p=0.002), compared to 79% (74–84%), respectively.

Abstract 28 Figure 1

Kaplan-Meier survival curves for recurrence-freesurvival in the fully triaged MMRd patients

Conclusion The prevalence of LS in the PORTEC EC trial population was 3% and within the MMRd group 10%. LS MMRd-EC seems to have a better overall and recurrence-free survival than sporadic MMRd-EC caused by hypermethylation. Further research into the underlying causes of non-hypermethylated somatic MMRd-EC is ongoing.

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