Integration of L1CAM and β-catenin immunohistochemistry for prognostic risk stratification of endometrial carcinoma: a practical approach for resource-limited settings.

Accurate prognostic stratification of endometrial carcinoma (EC) remains challenging in resource-limited settings lacking molecular sequencing. We investigated whether immunohistochemical (IHC) assessment of combined L1CAM/β-catenin expression, integrated with mismatch repair (MMR) status and p53 expression, could refine prognostic risk stratification in EC in absence of POLE sequencing. A retrospective cohort study evaluated 140 surgically staged EC cases for L1CAM, β-catenin MMR, and p53 IHC expression with clinicopathological correlation. Survival analysis was performed on 111 cases (median follow up:38 months). L1CAM and β-catenin demonstrated mutually exclusive expression patterns (27.1% and 6.4% respectively; 66.5% double negative). L1CAM + tumors demonstrated significantly worse disease specific survival (DSS) (HR:4, 95%CI: 1.6—9.9) and disease-free survival (DFS) (HR:4.9, 95%CI: 2.2–11.4), compared to double-negative (64.5% vs 90.3% DSS, 41.9% vs 12.5% relapse rate). β-catenin alone didn’t predict outcome but contributed to prognostic refinement when combined with L1CAM status. This prognostic gradient persisted in the pMMR/p53wt subgroup (L1CAM + mean DFS: 21.7 months vs double-negative: 69.6 months; p ≤ 0.001). The combined L1CAM/β-catenin IHC profile categorized patients into prognostically distinct categories and offers pragmatic prognostic refinement, particularly for pMMR/p53wt tumors in centers lacking POLE sequencing. This approach doesn’t replace comprehensive molecular testing and requires prospective validation before clinical implementation.