Objective: To study the characteristics of polymerase epsilon  (POLE ) exonuclease domain mutations in Chinese patients with endometrial carcinoma (EC).
Methods: This study analyzed data from 529 patients with EC in The Cancer Genome Atlas (TCGA) and 467 EC patients evaluated at the Shanghai First Maternity and Infant Hospital (SFMIH). POLE  mutation heterogeneity was analyzed in paired curettage and hysterectomy samples from 120 SFMIH patients. Sanger sequencing identified mutations in the POLE  exonuclease domain, and correlations between POLE  mutation status and various clinicopathological features were determined by chi-squared testing and Cohen’s kappa analysis, with Kaplan–Meier survival curves generated to assess correlations between POLE  mutation status and overall survival (OS).
Results: Thirty-five mutations were identified in 467 samples (7.5%), and novel mutations were detected in the SFMIH cohort. Compared to the TCGA cohort, the SFMIH cohort had fewer POLE  mutations when matched by age (< 60) and histology (endometrioid) (p < 0.001 and p = 0.010, respectively). In our study cohort, POLE  mutations were significantly associated with adjuvant treatment (p = 0.029), and patients with POLE  mutations who underwent chemoradiotherapy had a poor OS (p < 0.0001). Notably, shorter OS was significantly associated with POLE  mutations in hysterectomy samples from patients aged > 60 years or with stage I disease in the paired curettage-hysterectomy group.
Conclusion: The significant difference in POLE  mutation profiles between the TCGA and SFMIH cohorts, as well as the poor consistency between the curettage and hysterectomy samples, suggests that different parameters need to be applied to determine the prognosis of patients with EC in China.
Keywords: endometrial carcinoma, polymerase epsilon  mutation, POLE  mutation, Chinese cohort, hysterectomy, curettage specimens