The prognostic impact of molecular classification in endometrial cancer that undergoes fertility-sparing treatment

Int J Gynecol Cancer. 2025 Jan;35(1):100024. doi: 10.1016/j.ijgc.2024.100024. Epub 2024 Dec 18.

Abstract

Objective: No biomarkers are available to predict treatment response in patients with endometrial cancers who undergo fertility-sparing treatment. Therefore, we aimed to evaluate the prognostic role of molecular classification.

Methods: Patients with endometrial cancer who underwent fertility-sparing treatment with progestins between 2005 and 2021 were retrospectively identified. Polymerase epsilon (POLE), TP53/p53, and mismatch repair (MMR) proteins were assessed to assign patients to molecular groups: POLE mutated (POLEmut), MMR deficient (MMRd), no specific molecular profile (NSMP), and p53 abnormal (p53abn). Treatment response was classified as complete, partial, stable disease, or progressive. Response at 6 months, best response, and recurrence after complete response were evaluated by molecular class.

Results: In total, 33 patients were assigned to a molecular class and included in the analysis. Molecular testing detected 3 POLEmut (9%), 3 MMRd (9%), 25 NSMP (76%), and 2 p53abn (6%); 0 of 3 POLEmut (0%), 0 of 3 MMRd (0%), 6 of 25 NSMP (24%), and 1 of 2 p53abn (50%) achieved complete response within 6 months. In terms of best response during the entire treatment period, 2 of 3 POLEmut (67%), 2 of 3 MMRd (67%), 18 of 25 NSMP (72%), and 1 of 2 p53abn (50%) showed complete response. After complete response was achieved, 1 of 2 POLEmut (50%), 2 of 2 MMRd (100%), 14 of 18 NSMP (78%), and 0 of 1 p53abn (0%) had a recurrence.

Conclusion: Although the small number of patients limits our findings, a lower proportion of MMRd responded to progestins than of NSMP.

MeSH terms

  • Adult
  • DNA Mismatch Repair
  • DNA Polymerase II / genetics
  • Endometrial Neoplasms* / classification
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / pathology
  • Endometrial Neoplasms* / therapy
  • Female
  • Fertility Preservation* / methods
  • Humans
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Progestins / therapeutic use
  • Prognosis
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Tumor Suppressor Protein p53
  • DNA Polymerase II
  • TP53 protein, human
  • Progestins
  • Poly-ADP-Ribose Binding Proteins
  • POLE protein, human