子宫内膜癌的预后分层涉及分期、子宫危险因素和分子分类的评估。这个过程可以通过预后生物标志物的注释进一步完善，特别是 L1 细胞粘附分子 (L1CAM) 和激素受体。天冬酰胺酶样蛋白 1 (ASRGL1) 的缺失已被证明与子宫内膜癌的不良预后相关。我们的目标是结合其他可用方法评估 ASRGL1 对子宫内膜癌的预后。这是一项针对在单一三级中心接受初级治疗的患者的回顾性研究。通过子宫内膜癌主动分子风险分类器对肿瘤进行分子分类。通过免疫组织化学测定 ASRGL1、L1CAM、雌激素受体和孕激素受体的表达。 ASRGL1 表达强度分为四类。在 775 名患者的队列中，中位监测时间为 81 个月，ASRGL1 表达强度与改善的疾病特异性生存率呈剂量依赖性相关 (P < 0.001)。低表达水平与 II-IV 期疾病和子宫因素的存在相关，即高级别、淋巴管间隙侵犯和深肌层侵犯（所有 P < 0.001）。在分子亚组中，低表达在 p53 异常癌中最为普遍 (P < 0.001)。低 ASRGL1 与 L1CAM 阳性表达和雌激素和孕激素受体阴性表达相关（全部 P < 0.001）。调整分期和子宫因素后，强 ASRGL1 染色强度与癌症相关死亡风险较低相关（风险比 0.56，95% 置信区间 0.32-0.97；P = 0.038）。当根据分期、分子亚组、L1CAM 和激素受体进行调整后，ASRGL1 与结果无关。当在不同分子亚组中单独分析时，ASRGL1 显示与疾病特异性生存相关，特别是在“无特定分子特征”亚型癌症中（P < 0.001）。然而，在控制混杂因素后，这种关联变得不显着。ASRGL1 表达强度低与子宫内膜癌的生存率低相关。当控制分期和子宫因素时，ASRGL1 有助于更准确的预测。然而，当根据阶段和其他生物标志物（包括分子亚组）进行调整时，ASRGL1 不会改善预后分层。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Prognostic stratification of endometrial cancer involves the assessment of stage, uterine risk factors, and molecular classification. This process can be further refined through annotation of prognostic biomarkers, notably L1 cell adhesion molecule (L1CAM) and hormonal receptors. Loss of asparaginase-like protein 1 (ASRGL1) has been shown to correlate with poor outcome in endometrial cancer. Our objective was to assess prognostication of endometrial cancer by ASRGL1 in conjunction with other available methodologies.This was a retrospective study of patients who underwent primary treatment at a single tertiary center. Tumors were molecularly classified by the Proactive Molecular Risk Classifier for Endometrial Cancer. Expression of ASRGL1, L1CAM, estrogen receptor, and progesterone receptor was determined by immunohistochemistry. ASRGL1 expression intensity was scored into four classes.In a cohort of 775 patients, monitored for a median time of 81 months, ASRGL1 expression intensity was related to improved disease-specific survival in a dose-dependent manner (P < 0.001). Low expression levels were associated with stage II-IV disease and presence of uterine factors, i.e. high grade, lymphovascular space invasion, and deep myometrial invasion (P < 0.001 for all). Among the molecular subgroups, low expression was most prevalent in p53 abnormal carcinomas (P < 0.001). Low ASRGL1 was associated with positive L1CAM expression and negative estrogen and progesterone receptor expression (P < 0.001 for all). After adjustment for stage and uterine factors, strong ASRGL1 staining intensity was associated with a lower risk for cancer-related deaths (hazard ratio 0.56, 95 % confidence interval 0.32-0.97; P = 0.038). ASRGL1 was not associated with the outcome when adjusted for stage, molecular subgroups, L1CAM, and hormonal receptors. When analyzed separately within the different molecular subgroups, ASRGL1 showed an association with disease-specific survival specifically in "no specific molecular profile" subtype carcinomas (P < 0.001). However, this association became nonsignificant upon controlling for confounders.Low ASRGL1 expression intensity correlates with poor survival in endometrial cancer. ASRGL1 contributes to more accurate prognostication when controlled for stage and uterine factors. However, when adjusted for stage and other biomarkers, including molecular subgroups, ASRGL1 does not improve prognostic stratification.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.