Abstract：
OBJECTIVE: To assess the risk stratification of clinicopathologically and molecularly classified endometrial cancer based on estrogen receptor (ER) and L1 cell adhesion molecule (L1CAM) expression.
METHODS: This was a retrospective study of patients who underwent primary treatment at a single tertiary center. Carcinomas were classified into 5 clinicopathological risk groups, as per European guidelines. Immunohistochemistry and polymerase-ϵ sequencing were conducted for molecular classification and determination of ER and L1CAM expression.
RESULTS: Data from 1044 patients were analyzed. The median follow-up was 67.5 months. In univariable analyses, ER expression correlated with improved disease-specific survival (DSS) in the \"no specific molecular profile\" (NSMP) (P < 0.001) and mismatch repair deficient (MMRd) (P = 0.002) subgroups. Negative L1CAM expression was associated with enhanced DSS in the NSMP subgroup alone (P < 0.001). ER (hazard ratio [HR] 0.18), but not L1CAM, exhibited prognostic significance within NSMP when controlling for parameters available at the time of diagnosis (tumor histotype, grade, age). ER and L1CAM were not independently associated with DSS within NSMP when controlling for parameters available after surgery (clinicopathological risk groups, age, adjuvant therapy). However, in high-risk-advanced-metastatic cases, both ER (HR 0.26) and L1CAM (HR 3.9) independently correlated with DSS. Similarly, within MMRd, ER was associated with improved DSS in high-risk-advanced-metastatic carcinomas (HR 0.42).
CONCLUSIONS: The prognostic significance of ER and L1CAM varies across clinicopathological risk groups and molecular subgroups of endometrial cancer. Notably, risk assessment for high-risk-advanced-metastatic NSMP and MMRd subtype carcinomas can be refined by ER status.
METHODS: This was a retrospective study of patients who underwent primary treatment at a single tertiary center. Carcinomas were classified into 5 clinicopathological risk groups, as per European guidelines. Immunohistochemistry and polymerase-ϵ sequencing were conducted for molecular classification and determination of ER and L1CAM expression.
RESULTS: Data from 1044 patients were analyzed. The median follow-up was 67.5 months. In univariable analyses, ER expression correlated with improved disease-specific survival (DSS) in the \"no specific molecular profile\" (NSMP) (P < 0.001) and mismatch repair deficient (MMRd) (P = 0.002) subgroups. Negative L1CAM expression was associated with enhanced DSS in the NSMP subgroup alone (P < 0.001). ER (hazard ratio [HR] 0.18), but not L1CAM, exhibited prognostic significance within NSMP when controlling for parameters available at the time of diagnosis (tumor histotype, grade, age). ER and L1CAM were not independently associated with DSS within NSMP when controlling for parameters available after surgery (clinicopathological risk groups, age, adjuvant therapy). However, in high-risk-advanced-metastatic cases, both ER (HR 0.26) and L1CAM (HR 3.9) independently correlated with DSS. Similarly, within MMRd, ER was associated with improved DSS in high-risk-advanced-metastatic carcinomas (HR 0.42).
CONCLUSIONS: The prognostic significance of ER and L1CAM varies across clinicopathological risk groups and molecular subgroups of endometrial cancer. Notably, risk assessment for high-risk-advanced-metastatic NSMP and MMRd subtype carcinomas can be refined by ER status.
摘要：
目的：根据雌激素受体（ER）和L1细胞粘附分子（L1CAM）的表达评估子宫内膜癌的临床病理和分子分型危险分层。
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。将癌分为5个临床病理风险组，根据欧洲准则。进行免疫组织化学和聚合酶链反应测序以进行分子分类和ER和L1CAM表达的测定。
结果：分析了1044例患者的数据。中位随访时间为67.5个月。在单变量分析中，在“无特异性分子谱”（NSMP）（P<0.001）和错配修复缺陷（MMRd）（P=0.002）亚组中，ER表达与疾病特异性生存率（DSS）改善相关。在单独的NSMP亚组中，L1CAM阴性表达与DSS增强相关(P<0.001)。ER（危险比[HR]0.18），但不是L1CAM，在控制诊断时可用的参数时，在NSMP中表现出预后意义(肿瘤组织型，grade,年龄)。在控制手术后可用的参数时，ER和L1CAM与NSMP内的DSS并不独立相关（临床病理风险组，年龄,辅助治疗）。然而,在高风险晚期转移病例中，ER（HR0.26）和L1CAM（HR3.9）均与DSS独立相关。同样，在MMRd内,在高风险晚期转移性癌中，ER与改善的DSS相关（HR0.42）。
结论：ER和L1CAM的预后意义因子宫内膜癌的临床病理风险组和分子亚组而异。值得注意的是,对高危晚期转移性NSMP和MMRd亚型癌的风险评估可以通过ER状态进行细化.
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。将癌分为5个临床病理风险组，根据欧洲准则。进行免疫组织化学和聚合酶链反应测序以进行分子分类和ER和L1CAM表达的测定。
结果：分析了1044例患者的数据。中位随访时间为67.5个月。在单变量分析中，在“无特异性分子谱”（NSMP）（P<0.001）和错配修复缺陷（MMRd）（P=0.002）亚组中，ER表达与疾病特异性生存率（DSS）改善相关。在单独的NSMP亚组中，L1CAM阴性表达与DSS增强相关(P<0.001)。ER（危险比[HR]0.18），但不是L1CAM，在控制诊断时可用的参数时，在NSMP中表现出预后意义(肿瘤组织型，grade,年龄)。在控制手术后可用的参数时，ER和L1CAM与NSMP内的DSS并不独立相关（临床病理风险组，年龄,辅助治疗）。然而,在高风险晚期转移病例中，ER（HR0.26）和L1CAM（HR3.9）均与DSS独立相关。同样，在MMRd内,在高风险晚期转移性癌中，ER与改善的DSS相关（HR0.42）。
结论：ER和L1CAM的预后意义因子宫内膜癌的临床病理风险组和分子亚组而异。值得注意的是,对高危晚期转移性NSMP和MMRd亚型癌的风险评估可以通过ER状态进行细化.
