- 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.