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Prognostic values of molecular subtypes and SWI/SNF protein expression in de-differentiated/undifferentiated endometrial carcinoma

  • 0Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Histopathology +

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January 15, 2025

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January 15, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Molecular classification of endometrial cancer (EC) is evolving. In rare de-differentiated/undifferentiated EC (DD/UDEC), only POLE-mutant tumors show good outcomes; other subtypes (MMRd, p53abn, NSMP) have poor prognoses.

Area Of Science

  • Gynecologic Oncology
  • Molecular Pathology
  • Cancer Genomics

Background

  • Endometrial carcinoma (EC) classification has shifted from histopathology to molecular subtypes (POLEmut, MMRd, NSMP, p53abn) with distinct prognoses.
  • The utility of molecular classification in rare, aggressive EC histotypes like de-differentiated/undifferentiated EC (DD/UDEC) remains unclear.

Purpose Of The Study

  • To investigate the prognostic significance of molecular subtypes (ProMisE classifier) in a cohort of DD/UDEC.
  • To analyze the expression of SWI/SNF chromatin remodelling complex members in DD/UDEC and their potential prognostic value.

Main Methods

  • Retrospective analysis of 88 DD/UDEC cases from a single institution.
  • Molecular subtyping using POLE sequencing and immunohistochemistry for p53, mismatch repair proteins, and SWI/SNF proteins (ARID1A, ARID1B, SMARCA4, SMARCA2).

Main Results

  • Molecular subtypes were assigned in 80 DD/UDEC cases: 15% POLEmut, 55% MMRd, 17.5% p53abn, 12.5% NSMP.
  • POLEmut DD/UDEC exhibited excellent outcomes, while MMRd, p53abn, and NSMP subtypes showed uniformly poor prognoses.
  • Loss of SWI/SNF proteins (66% of cases) did not significantly impact prognosis.

Conclusions

  • In DD/UDEC, all molecular subtypes except POLEmut are associated with aggressive behavior.
  • Further research is needed to explore targeted adjuvant therapies for DD/UDEC based on molecular alterations to improve patient outcomes.

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