Article Text

Download PDFPDF

EP182/#276  Molecular characterization of stage I, grade 3 endometrioid endometrial cancer
  1. Bill Zammarrelli1,
  2. Arrnaud Da Cruz Paula2,
  3. Beryl Manning-Geist1,
  4. Sarah Kim1,
  5. Mario Leitao1,
  6. Nadeem Abu-Rustum1,
  7. Vicky Makker3,
  8. Lora Ellenson2,
  9. Jennifer Mueller1 and
  10. Britta Weigelt2
  1. 1Memorial Sloan Kettering Cancer Center, Gynecology Service, Department of Surgery, New York, USA
  2. 2Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, USA
  3. 3Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, USA


Introduction Endometroid endometrial cancers (EECs) are clinically and molecularly heterogeneous. We sought to investigate the molecular landscape of stage I, grade 3 EECs.

Methods Patients with stage I, grade 3 EECs who underwent surgical staging from 1/2014–1/2020 were identified. Clinicopathologic data were curated from electronic medical records. All EECs underwent tumor-normal targeted panel sequencing of up to 505 cancer-related genes and were classified by molecular subtype. POLE-mutated ECCs were excluded from mutational analyses, as they are ultramutated tumors.

Results Seventy-five patients were identified. Unlike stage I, grade 1 EECs, which are mostly of copy number (CN)-low molecular subtype, most of our stage I, grade 3 EECs were of POLE (25/75, 33%) or microsatellite instability (MSI)-high (24/75, 32%) molecular subtypes; 20% (15/75) were CN-high and 15% (11/75) CN-low. Patients with MSI-high EECs, compared to other subtypes, were more likely to have deep myometrial invasion (p=0.02) and to have received chemotherapy (p=0.01). After exclusion of POLE EECs, 50 patients met criteria for mutational analyses. The most common alterations affected PTEN (68%), ARID1A (46%), PIK3CA (42%), and PIK3R1 (38%). Stage I, grade 3 EECs with positive lymphovascular space invasion, compared to those without, more frequently harbored PTEN (86% vs 56%, p=0.03), PIK3R1 (57% vs 28%, p=0.04), and MAP2K4 (19% vs 0%, p=0.03) mutations. Stage IB cases, compared to stage IA cases, were more likely to harbor FBXW7 (29% vs 6%, p=0.04) and KMT2D (64% vs 25%, p=0.02) mutations.

Conclusion/Implications Stage I, grade 3 EECs are a heterogenous group of tumors with varying mutational profiles and molecular subtypes.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.