Prevalence and Survival Outcomes of L1 Cell Adhesion Molecule–Positive in Endometrial Cancer Across Molecular Subtypes: A Systematic Review and Meta-Analysis

PURPOSE L1 cell adhesion molecule (L1CAM) has emerged as a potential prognostic biomarker in endometrial cancer. This systematic review and meta-analysis aimed to comprehensively evaluate the prevalence of L1CAM expression across molecular subtypes of endometrial cancer and its prognostic significance for survival outcomes. MATERIALS AND METHODS A systematic literature search of PubMed, Embase, and Cochrane Library was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies reporting L1CAM expression in endometrial cancer, stratified by molecular subtypes (polymerase epsilon [POLE], mismatch repair deficiency [MMR-D], no specific molecular profile [NSMP], p53 wild type [p53wt], p53 abnormal [p53abn]), and their association with survival outcomes were included. Pooled prevalence and hazard ratios with 95% CIs were calculated using random-effects models. RESULTS Twenty-one retrospective studies met the inclusion criteria. The overall pooled prevalence of L1CAM positivity was 15%. Stratified by molecular subtype, prevalence was the lowest in POLE-mutated tumors (4.87%), followed by p53abn tumors (52.86%), MMR-D tumors (52.16%), NSMP (30.88%), and p53wt (25.99%). L1CAM positivity was significantly associated with worse disease-specific survival (hazard ratio [HR], 2.49 [95% CI, 1.75 to 3.55]) and progression-free survival (HR, 2.50 [95% CI, 1.56 to 4.01]). Subgroup analyses revealed significant associations in MMR-D tumors (HR, 1.75 [95% CI, 1.06 to 2.89]), NSMP tumors (HR, 5.41 [95% CI, 2.92 to 10.03]), and a borderline effect in p53abn tumors (HR, 1.69 [95% CI, 1.00 to 2.85]). CONCLUSION The highest prevalence of L1CAM was found in p53abn endometrial tumors. L1CAM positivity is associated with poor survival outcomes, particularly in MMR-D and NSMP subgroups. These findings highlight the potential of L1CAM as a prognostic biomarker that could refine risk stratification and guide adjuvant management more accurately in endometrial cancer, warranting validation in prospective studies.