目的:子宫内膜癌的预后分层涉及分期评估,子宫危险因素,和分子分类。这一进程可经由过程对预后生物标志物的注释进一步细化,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)的缺失与子宫内膜癌的不良预后相关。我们的目标是通过ASRGL1结合其他可用方法评估子宫内膜癌的预后。
方法:这是一项对在单一三级中心接受初级治疗的患者的回顾性研究。根据子宫内膜癌的前分子风险分类法对肿瘤进行分子分类。ASRGL1、L1CAM、雌激素受体,用免疫组织化学方法测定孕激素受体。ASRGL1表达强度分为四类。
结果:在775名患者的队列中,监测的中位时间为81个月,ASRGL1表达强度与改善疾病特异性生存率呈剂量依赖性(P<0.001)。低表达水平与II-IV期疾病和子宫因子的存在有关,即高品位,淋巴管间隙侵入,和深肌层浸润(均P<0.001)。在分子亚组中,低表达在p53异常癌中最普遍(P<0.001)。低ASRGL1与L1CAM表达阳性和雌激素和孕激素受体表达阴性相关(均P<0.001)。在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).经分期调整后,ASRGL1与结果无关,分子亚群,L1CAM,和激素受体。当在不同的分子亚组内分别分析时,ASRGL1在“无特定分子谱”亚型癌中显示出与疾病特异性生存相关(P<0.001)。然而,在控制混杂因素后,这种关联变得不重要.
结论:低ASRGL1表达强度与子宫内膜癌的低生存率相关。当控制分期和子宫因素时,ASRGL1有助于更准确的预测。然而,当调整阶段和其他生物标志物时,包括分子亚组,ASRGL1不能改善预后分层。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.