Clinicopathologic Evaluation of CTNNB1 Mutations in High-Intermediate Risk Endometrial Endometrioid Carcinoma

CTNNB1 mutations convey increased risk of recurrence in low-risk endometrial endometrioid carcinoma (EEC). Results from previous high-intermediate risk (HIR) cohorts are mixed. The aims of this study were to correlate CTNNB1 mutational status with clinical outcomes and to evaluate the relationship between CTNNB1 mutations and the 4 prognostic subgroups defined by The Cancer Genome Atlas in HIR EEC. CTNNB1 mutational status was determined by Sanger sequencing of exon 3 of the CTNNB1 gene. Mismatch repair, POLE, p53, and L1 cell-adhesion molecule (L1CAM) status were also evaluated. Descriptive statistics and survival analyses were performed. Eighty-eight cases of HIR EEC were identified, of which 22 (25%) were CTNNB1 mutant (CTNNB1-mut) and 66 (75%) were wild-type (CTNNB1-WT). Median follow-up was 60 mo. Recurrence occurred in 13/88 (15%) patients. Recurrence rates were not significantly different between patients with CTNNB1-mut and CTNNB1-WT tumors (14% vs. 15%, P=0.86). Recurrence-free survival and overall survival were not significantly different (recurrence-free survival hazard ratio: 0.97, 95% confidence interval: 0.27-3.52, P=0.96; overall survival hazard ratio: 0.23, 95% confidence interval: 0.03-1.71, P=0.15). Mismatch repair deficiency was more prevalent in CTNNB1-WT compared with CTNNB1-mut tumors (46% vs. 14%, P=0.01); prevalence of POLE mutations and aberrant p53 were not significantly different. In contrast to patients with low-risk EEC, no differences in recurrence or survival were found in patients with HIR EEC with CTNNB1-mut compared with CTNNB1-WT tumors.