High-Intermediate Risk Endometrial Cancer: Can Gene Expression Predict Recurrence?


Cindy Tawfik, BA, Angelina I. Londoño, PhD, Allison Montgomery, BS, Alba Martinez, MS, Katherine A. Shelton, BS, Beomjy Kim, BS, Ashwini A. Katre, MS, Warner K. Huh, MD, Eddy Yang, MD, PhD, Kerri S. Bevis, MD, MSPH, J. Michael Straughn, Jr., MD, Charles A. Leath III, MD, Rebecca C. Arend, MD


  • Endometrial cancer (EMCA) is the most common gynecologic cancer in the United States.
  • Most cases are diagnosed at Stage 1 and have an excellent prognosis after surgery alone.
  • A subset of early-stage endometrial cancer patients are at higher risk for recurrence.
  • Prognostic factors of recurrence of early stage EMCA include lymphovascular space invasion (LVSI), histologic grade (2 or 3), depth of myometrial invasion (>50%), and patient age.
  • Results from GOG 99 and PORTEC-2 led to the designation of a subset of patients known as highintermediate risk (H-IR) EMCA based on reproducible pathologic risk factors.
  • H-IR EMCA patients are at 20-30% risk of recurrence even in the setting of early stage disease.
  • Studies have shown that adjuvant therapy increases progression free survival, but does not affect overall survival in these patients


To identify a gene signature that determines which H-IR EMCA patients are at the highest risk for recurrence and to identify RNA expression changes that occur in the recurrent tumor.


  • Similar number and type of DNA mutations were found in patients that recurred compared to matching patients that did not recur.
  • MSI-High and mutations in JAK1, DICER1, BRD3, PMS2, PDE4DIP, and BCOR genes were more comely observed in patients that recurred.
  • RNA expression pathway analysis of EMCA patients that recurred vs matched patients that did not recur resulted in 2 pathways that were significantly up regulated in the patients that recurred: Cell Cycle and DNA Damage.
  • Nine of 13 pathways were significantly altered in tissue samples from the time of recurrence compared to tissue from the time of diagnosis.
  • The results of this study are hypothesis generating and will need to be validated in a much larger cohort.
  • These findings could potentially impact the decision to treat H-IR EMCA patients with adjuvant therapy.

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