Objectives To characterize the genomic alterations in recurrent low-grade, non-invasive endometrioid endometrial carcinomas (EECs).
Methods We retrospectively identified patients with stage IA EEC who underwent primary surgery at our institution, 2/2009–2/2017, and had follow-up of at least 11 months. “Ultra-low risk” was defined as FIGO grade 1/2, non-invasive, and lymphovascular space invasion-negative. DNA extracted from 36 tumors and matched normal tissue/blood was subjected to massively parallel sequencing targeting over 400 cancer-related genes. Microsatellite instability was assessed via MSIsensor.
Results 499 patients with “ultra-low risk” EEC were identified. 14/499 (2.8%) had a recurrence. Median follow-up for non-recurrent cases was 33.0 months (range, 11–116) and for recurrent 50.5 months (range, 11–116). Recurrent patients were older than non-recurrent patients (p=0.016), and had endometriosis identified during pathologic review of specimen more frequently (p=0.015). Other clinical characteristics did not differ.
Mutational profiling of primary tumors from 8 recurrent and 28 non-recurrent patients revealed that most ultra-low risk EECs were microsatellite-stable (7/8, 88% recurrent; 26/28, 93% non-recurrent). Mutational signatures varied widely with no dominant signature identified among either group. PTEN and PIK3CA were the most frequently mutated genes in both groups. CTNNB1 hotspot mutations were found in 4/8 (50%) recurrent and 9/28 (33%) non-recurrent EECs (p=0.146).
Conclusions Patients diagnosed with “ultra-low risk” EEC have an excellent prognosis; however, we noted that 2.8% of patients developed a recurrence without identifiable clinical or pathologic risk factors. Genomic profiling did not reveal unique alterations in either group. Further work is needed to elucidate the mechanism/biomarker for recurrence in this “ultra-low risk” population.
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