Genomic Profiling Of High-Intermediate Risk Endometrial Cancer To Differentiate Recurrence Risk.

e17103 Background: While the majority of patients diagnosed with endometrial cancer (EMCA) have low-risk disease at the time of diagnosis, a subset of patients with Stage I disease are classified as high-intermediate risk (H-IR) based on pathologic risk factors. H-IR EMCA patients have a 30% risk of recurrence. While adjuvant therapy may improve progression free survival, there is limited data to suggest an improvement in overall survival. Methods: Under IRB approval we performed a pilot study isolating the RNA from paraffin embedded tissue from 16 patients who underwent surgery at UAB between July 2000 and November 2010. All patients met criteria for H-IR EMCA which included presence of 1-3 pathologic risk factors: a) outer 1/2 or 1/3 myometrial invasion; b) presence of LVSI; c) grade 2 or 3 tumor. No patient received adjuvant therapy after surgery. We selected 8 patients who recurred within 3 years and 8 controls who did not have a recurrence. Patients were matched for stage, grade, race, age, presence or absence of LVSI, depth of invasion, and size of tumor. RNA expression of the two groups were compared using the NanoString platform utilizing the nCounter PanCancer Pathways Panel (770 genes). Data was analyzed using the nSolver Software and Ingenuity Pathway Analysis (IPA). Results: Using a fold change of greater than or equal to ± 1.5 and a p-value of < 0.05, 10 genes were significantly up-regulated (2 to 6 fold) in H-IR EMCA patients that recurred: MMP3, INHBB, TNF, NR4A, PLA2G3, CLCF1, LAMB3, RAD51, FOS, LEFTY2. Two genes were significantly down-regulated (1.5 fold): COL27A1 and BAIAP3. Five pathways were statistically different between the two groups using IPA: Aryl hydrocarbon receptor signaling, cyclins and cell cycle regulation pathway, bladder cancer signaling pathway, colorectal cancer metastasis pathway, and rheumatoid arthritis pathway. Conclusions: This pilot study identified significantly differentially expressed genes in patients with H-IR EMCA who experience a recurrence compared to those patients that do not recur. Based on these findings, it may be possible to develop a genetic signature to identify patients that may benefit from adjuvant therapy rather than using pathologic criteria alone.