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Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently,  CTNNB1  exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of  CTNNB1  mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers.  CTNNB1  exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in  CTNNB1  exon 3. Nuclear beta-catenin and LEF1 were significantly associated with  CTNNB1  mutation, showing nuclear beta-catenin a better specificity and positive predictive value for  CTNNB1  mutation. Tumours with  CTNNB1  exon 3 mutation were associated with reduced disease-free survival ( p  = 0.010), but no impact on overall survival was found ( p  = 0.807). The risk of relapse in tumours with  CTNNB1  exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion.  CTNNB1  exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for  CTNNB1  exon 3 mutation in these tumours. Graphical abstract

Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma