Integration of L1CAM and β-catenin immunohistochemistry for prognostic risk stratification of endometrial carcinoma: a practical approach for resource-limited settings.
Sara Eldegwi, Basma Gadelhak, Nadia Bassiouny, Mohamed Fawzy, Khadiga M Ali
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引用次数: 0
Abstract
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.
期刊介绍：
Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization.
Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.
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