Evaluation of prognostic potential of ß-catenin and L1CAM expression according to endometrial cancer risk group.

ABSTRACT

OBJECTIVE: We investigate the prognostic role of ß-catenin and L1 neuronal cell-adhesion molecule (L1CAM) according to risk groups in endometrial carcinomas (EC). METHODS: A total of 335 EC patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer. We evaluated the expression of ß-catenin and L1CAM using immunohistochemistry, and their association with clinicopathological characteristics and survival. RESULTS: The expressions of ß-catenin and L1CAM were observed in 10.4% of all patients, respectively, and showed mutually exclusive pattern. While ß-catenin expression was associated with endometrioid histology (p = 0.035) and low tumor grade (p = 0.045), L1CAM expression was associated with non-endometrioid histology (p < 0.001), high tumor grade (p < 0.001), lymphovascular space invasion (p = 0.006), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.001). ß-catenin expression was most frequent in the no specific molecular (NSMP) group (26/35, 74.3%), followed by the DNA polymerase-ε-mutated (POLE-mut) (6/35, 17.1%), and mismatch repair-deficiency (dMMR) (3/35, 8.6%). L1CAM expression was most frequent in the p53-abnormal group (22/35, 62.9%), followed by the NSMP (6/35, 17.1%), dMMR (4/35, 11.4%), and POLE-mut (3/35, 8.6%). Although both markers did not show statistical significance in multivariate analysis for both progression-free survival (PFS) and overall survival in entire cohort, ß-catenin positivity was identified as the sole factor associated with worse PFS in the high-intermediate risk subgroup (p = 0.001). CONCLUSION: The expression of nuclear ß-catenin may serve as a potential biomarker for predicting recurrence and guiding therapeutic strategies in high-intermediate risk EC patients.