Dr Cun on Molecular Classification in Endometrioid Endometrial Adenocarcinoma

Han T. Cun, MD, MS, gynecologic oncology fellow, The University of Texas MD Anderson Cancer Center, discusses the findings from a retrospective comprehensive molecular classification of patients with grade 3 endometrioid endometrial adenocarcinoma.

This study included 46 patients from 2 institutions with deeply invasive, node-negative, stage IB, grade 3 endometrioid endometrial adenocarcinoma who underwent surgical staging between 2005 and 2017. From archival tissue from these patients, the investigators extracted and isolated DNA for whole-exome sequencing and performed immunohistochemistry staining for mismatch repair (MMR) proteins and p53 mutations. From these characterization methods, the investigators stratified the patients by their clinicopathologic features per ProMisE v2 classification, Cun says.

In total, 21.7% (n = 10), 39.1% (n = 18), 13.0% (n = 6), and 26.1% (n = 12) of patients had POLE mutations, MMR-deficient (dMMR) disease, abnormal p53 expression, and p53 wild-type disease, respectively. The median age in all patients was 66.8 years, and the median ages were similar across the patient subgroups, at 62.6 years, 66.5 years, 72.3 years, and 68.0 years in the POLE mutation, dMMR, abnormal p53, and p53 wild-type subgroups, respectively.

However, the patient subgroups differed the most regarding mean body mass index (BMI) and race. In all patients, the mean BMI was 30.7 kg/m², and in the POLE mutation, dMMR, abnormal p53, and p53 wild-type subgroups, the mean BMIs were 25.9 kg/m², 31.3 kg/m², 32.2 kg/m², and 32.9 kg/m², respectively. Additionally, 93.5% (n = 43) and 6.5% (n = 3) of all patients were White and Hispanic, respectively. Across the POLE mutation, dMMR, abnormal p53, and p53 wild-type subgroups, 90% (n = 9), 100% (n = 18), 83.3% (n = 5), and 91.7% (n = 11) of patients were White, respectively.

In total, 74% of patients received adjuvant therapy. Almost 20% of patients (n = 9) had disease recurrence, 5 of whom had extra-abdominal recurrence. No patients with POLE mutations recurred. Across the whole population, the mean time to recurrence was 20.8 months (range, 4-36.7).

Among the subgroups, the investigators observed no difference in median recurrence-free survival (P = .22) and a statistically significant difference in overall survival (OS; P = .017). The median OS was 52.4 months in the abnormal p53 subgroup and 40.5 months in the p53 wild-type subgroup and was not reached in the POLE mutation and dMMR subgroups.