Pradhan Manohar, Kildal Wanja, Vlatkovic Ljiljana, Tobin Kari Anne R, Lindemann Kristina, Kristensen Gunnar B, Kleppe Andreas, Askautrud Hanne A
Oslo University Hospital, Division of Cancer Medicine, Institute for Cancer Genetics and Informatics, Oslo, Norway.
Oslo University Hospital, Division of Cancer Medicine, Institute for Cancer Genetics and Informatics, Oslo, Norway.
Int J Gynecol Cancer. 2025 Jul;35(7):101915. doi: 10.1016/j.ijgc.2025.101915. Epub 2025 May 3.
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.
三级淋巴结构是在癌症或慢性疾病刺激下形成的淋巴样细胞簇，在包括子宫内膜癌在内的多种癌症类型中作为一种预后标志物。我们使用替代标志物L1细胞粘附分子（L1CAM）评估了1208例处于所有分期、组织学亚型和风险组的子宫内膜癌患者中三级淋巴结构的预后意义。对每位患者的1个组织切片进行L1CAM免疫组化评估，结果显示1208例中有287例（23.8%）呈三级淋巴结构阳性。在单变量分析中，与无三级淋巴结构肿瘤的患者相比，三级淋巴结构阳性肿瘤患者的复发时间显著更长（风险比0.61，p <.001），癌症特异性生存率也显著更高（风险比0.53，p <.001）。在包含标准临床和病理标志物以及现代分子分类的多变量分析中，三级淋巴结构的存在是复发时间（风险比0.63，p <.001）和癌症特异性生存（风险比0.54，p <.001）的独立预后标志物。与p53异常（15.8%）和无特定分子特征（14.7%）的肿瘤相比，POLE突变（59.4%）和错配修复缺陷（32.3%）的肿瘤中三级淋巴结构的存在更为常见。在p53异常肿瘤的患者中，多变量分析显示三级淋巴结构的存在与复发时间（风险比0.51，p = 0.014）和癌症特异性生存（风险比0.52，p = 0.021）的更好结局均显著相关。这些发现表明，通过L1CAM评估三级淋巴结构可能提高子宫内膜癌的预后准确性。
