Abstract：
We investigate the prognostic role of β-catenin and L1 neuronal cell-adhesion molecule (L1CAM) according to risk groups in endometrial carcinomas (EC).
A total of 335 EC patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer. We evaluated the expression of ß-catenin and L1CAM using immunohistochemistry, and their association with clinicopathological characteristics and survival.
The expressions of β-catenin and L1CAM were observed in 10.4% of all patients, respectively, and showed mutually exclusive pattern. While β-catenin expression was associated with endometrioid histology (p = 0.035) and low tumor grade (p = 0.045), L1CAM expression was associated with non-endometrioid histology (p < 0.001), high tumor grade (p < 0.001), lymphovascular space invasion (p = 0.006), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.001). β-catenin expression was most frequent in the no specific molecular (NSMP) group (26/35, 74.3%), followed by the DNA polymerase-ε-mutated (POLE-mut) (6/35, 17.1%), and mismatch repair-deficiency (dMMR) (3/35, 8.6%). L1CAM expression was most frequent in the p53-abnormal group (22/35, 62.9%), followed by the NSMP (6/35, 17.1%), dMMR (4/35, 11.4%), and POLE-mut (3/35, 8.6%). Although both markers did not show statistical significance in multivariate analysis for both progression-free survival (PFS) and overall survival in entire cohort, β-catenin positivity was identified as the sole factor associated with worse PFS in the high-intermediate risk subgroup (p = 0.001).
The expression of nuclear β-catenin may serve as a potential biomarker for predicting recurrence and guiding therapeutic strategies in high-intermediate risk EC patients.
A total of 335 EC patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer. We evaluated the expression of ß-catenin and L1CAM using immunohistochemistry, and their association with clinicopathological characteristics and survival.
The expressions of β-catenin and L1CAM were observed in 10.4% of all patients, respectively, and showed mutually exclusive pattern. While β-catenin expression was associated with endometrioid histology (p = 0.035) and low tumor grade (p = 0.045), L1CAM expression was associated with non-endometrioid histology (p < 0.001), high tumor grade (p < 0.001), lymphovascular space invasion (p = 0.006), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.001). β-catenin expression was most frequent in the no specific molecular (NSMP) group (26/35, 74.3%), followed by the DNA polymerase-ε-mutated (POLE-mut) (6/35, 17.1%), and mismatch repair-deficiency (dMMR) (3/35, 8.6%). L1CAM expression was most frequent in the p53-abnormal group (22/35, 62.9%), followed by the NSMP (6/35, 17.1%), dMMR (4/35, 11.4%), and POLE-mut (3/35, 8.6%). Although both markers did not show statistical significance in multivariate analysis for both progression-free survival (PFS) and overall survival in entire cohort, β-catenin positivity was identified as the sole factor associated with worse PFS in the high-intermediate risk subgroup (p = 0.001).
The expression of nuclear β-catenin may serve as a potential biomarker for predicting recurrence and guiding therapeutic strategies in high-intermediate risk EC patients.
摘要：
目的：我们根据子宫内膜癌（EC）的风险组研究β-catenin和L1神经元细胞粘附分子（L1CAM）的预后作用。
方法：根据子宫内膜癌前发分子风险分类法对总共335例EC患者进行分类。我们使用免疫组织化学评估β-catenin和L1CAM的表达，以及它们与临床病理特征和生存率的关系。
结果：在所有患者中观察到10.4％的β-catenin和L1CAM表达，分别,并显示出相互排斥的模式。而β-catenin的表达与子宫内膜样组织学（p=0.035）和低肿瘤分级（p=0.045）有关，L1CAM表达与非子宫内膜样组织学相关(p<0.001),肿瘤分级高（p<0.001），淋巴管间隙侵犯（p=0.006），和先进的国际妇产科联合会（FIGO）阶段（p=0.001）。β-catenin在非特异性分子(NSMP)组中表达最频繁(26/35,74.3%),其次是DNA聚合酶-ε-突变（POLE-mut）（6/35，17.1%），和错配修复缺陷（dMMR）（3/35，8.6%）。L1CAM表达在p53异常组中最常见（22/35，62.9%），其次是NSMP（6/35，17.1%），DMMR（4/35，11.4%），和POLE-mut（3/35，8.6%）。尽管在整个队列的无进展生存期（PFS）和总生存期的多变量分析中，两种标志物均未显示统计学意义，β-连环蛋白阳性被确定为高-中等风险亚组PFS较差的唯一相关因素(p=0.001)。
结论：核β-catenin的表达可作为预测中高风险EC患者复发和指导治疗策略的潜在生物标志物。
方法：根据子宫内膜癌前发分子风险分类法对总共335例EC患者进行分类。我们使用免疫组织化学评估β-catenin和L1CAM的表达，以及它们与临床病理特征和生存率的关系。
结果：在所有患者中观察到10.4％的β-catenin和L1CAM表达，分别,并显示出相互排斥的模式。而β-catenin的表达与子宫内膜样组织学（p=0.035）和低肿瘤分级（p=0.045）有关，L1CAM表达与非子宫内膜样组织学相关(p<0.001),肿瘤分级高（p<0.001），淋巴管间隙侵犯（p=0.006），和先进的国际妇产科联合会（FIGO）阶段（p=0.001）。β-catenin在非特异性分子(NSMP)组中表达最频繁(26/35,74.3%),其次是DNA聚合酶-ε-突变（POLE-mut）（6/35，17.1%），和错配修复缺陷（dMMR）（3/35，8.6%）。L1CAM表达在p53异常组中最常见（22/35，62.9%），其次是NSMP（6/35，17.1%），DMMR（4/35，11.4%），和POLE-mut（3/35，8.6%）。尽管在整个队列的无进展生存期（PFS）和总生存期的多变量分析中，两种标志物均未显示统计学意义，β-连环蛋白阳性被确定为高-中等风险亚组PFS较差的唯一相关因素(p=0.001)。
结论：核β-catenin的表达可作为预测中高风险EC患者复发和指导治疗策略的潜在生物标志物。
