Prognostic value of tertiary lymphoid structures in molecular subgroups of endometrial carcinoma

Tertiary lymphoid structures, lymphoid cell clusters formed in response to cancer or chronic disease, serve as a prognostic marker in multiple cancer types, including endometrial carcinoma. We assessed the prognostic significance of tertiary lymphoid structures, using the surrogate marker L1 cell adhesion molecule (L1CAM), in 1208 endometrial carcinoma patients in all stages, histological subtypes, and risk groups. Immunohistochemical evaluation of L1CAM in 1 tissue section from each patient revealed tertiary lymphoid structure-positivity in 287 of 1208 (23.8%) cases. In univariable analyses, patients with tertiary lymphoid structure-positive tumors had significantly longer time to recurrence (HR 0.61, p < .001) and cancer-specific survival (HR 0.53, p < .001) compared to patients with tumors without tertiary lymphoid structures. In multivariable analyses with standard clinical and pathological markers as well as modern molecular classification, the presence of tertiary lymphoid structures was an independent prognostic marker for time to recurrence (HR 0.63, p < .001) and cancer-specific survival (HR 0.54, p < .001). The presence of tertiary lymphoid structures was more frequent in POLE-mutated (59.4%) and mismatch repair deficient (32.3%) compared to p53-abnormal (15.8%) and no specific molecular profile (14.7%) tumors. In patients with p53-abnormal tumors, the presence of tertiary lymphoid structures was significantly associated with better outcomes for both time to recurrence (HR 0.51, p = .014) and cancer-specific survival (HR 0.52, p = .021) in multivariable analyses. These findings suggest that the evaluation of tertiary lymphoid structures by L1CAM may enhance prognostic precision in endometrial carcinoma.