High grade endometrioid endometrial cancer (HGEEC) is a heterogeneous group of tumors with unclear prognostic features. The aim of the present study is to evaluate the independent risk factors for recurrence and mortality and to describe the recurrence patterns of HGEEC. Ninety-six consecutive cases of HGEEC treated with primary surgery in a single Tertiary Center were retrospectively reviewed. Clinicopathological and treatment details were recorded, and all patients were closely followed up. Disease-free, overall and cancer-specific survival rates were 83.8%, 77.8% and 83.6%, respectively. Cervical stromal involvement was independently related to recurrence (HR = 25.67; 95%CI 2.95–223.30; p = 0.003) and cancer-related death (HR = 15.39; 95%CI 1.29–183.43; p = 0.031) after adjusting for other pathological and treatment variables. Recurrence rate was 16%, with 60% of these cases having lung metastases and only one case with single vaginal vault recurrence. 81.81% of the recurrences presented with symptoms and not a single recurrence was diagnosed in routine follow-up clinical examination. In conclusion, the recurrence pattern may suggest that patient-initiated follow-up (PIFU) could be considered a potential alternative to clinical-based follow-up for HGEEC survivors, especially for patients without cervical involvement and after two years from treatment. Additional caution is needed in patients with cervical stromal involvement.
an NGS panel, identifying challenges in case classification and possible solutions. Methodology We performed the FoundationOne CDx NGS panel on 60 EC and assigned molecular subtype: POLE mutated (POLEmut), mismatch repair deficient (MMRd), p53 abnormal (p53abn) or no specific molecular subtype (NSMP). Result(s)* In 55 patients the molecular classification was successful. A pathogenic POLE mutation was detected in 9 cases (POLEmut). 20 were MMRd (12 MSI-high, 8 MSI-indeterminate based on the NGS panel MSI classifier) and a known or likely MMR gene mutation was found in 7 of these. Of the remaining 26 cases, 17 carried a TP53 mutation (p53abn) and the remaining 9 were considered to be NSMP. The tumor mutation burden (TMB) was significantly different (p<0.001) in the molecular subtypes (A) and high TMB (>55 mut/MB) was 100% specific for POLEmut EC (p<0.001). High TMB was specific for known pathogenic POLE mutations and was not elevated in cases with solely non-pathogenic POLE mutations (B).In non-POLEmut cases, TMB was higher in MSI-high and MSI-indeterminate than microsatellite stable (MSS) cases (C), and a TMB of >7 mut/MB was 100% specific for MMRd EC. There was one MSS EC with a TMB of 18 mut/MB but it showed loss of MLH1 and PMS2 proteins on immunostaining and was classified as MMRd. Conclusion* An NGS panel can be used in the molecular classification of EC when there is sufficient tumor cellularity. TMB can be used as an adjunct in molecular subtype diagnosis for tumors that are difficult to classify. Additionally, TMB can potentially serve as a diagnostic adjunct in cases with POLE mutation of unknown significance.
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