Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers

Gynecol Oncol. 2019 Jun;153(3):517-520. doi: 10.1016/j.ygyno.2019.03.100. Epub 2019 Mar 22.


Objectives: Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence.

Methods: A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing.

Results: 15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, p = 0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, p = 0.03). POLE mutations were found in 0% of cases vs. 7% of controls (p = 0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (p < 0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (p < 0.001).

Conclusions: Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population.

Keywords: Endometrial cancer; Molecular testing; Risk-stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Endometrioid / genetics*
  • Carcinoma, Endometrioid / pathology
  • Case-Control Studies
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • DNA Polymerase II / genetics
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Membrane Proteins / genetics
  • Microsatellite Instability
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Tumor Suppressor Protein p53 / genetics
  • beta Catenin / genetics*


  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Membrane Proteins
  • Poly-ADP-Ribose Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • DNA Polymerase II
  • POLE protein, human
  • TPTE protein, human
  • PTEN Phosphohydrolase