Aim: In order to enhance risk stratification in early-stage endometrial cancer (EC), we conducted molecular classification using surrogate markers, including thePOLEdroplet digital polymerase chain reaction (ddPCR) and L1CAM immunohistochemistry (IHC). Method: We analyzed archival tumor tissue from 183 early-stage EC patients.POLEpathogenic mutations of P286R, V411L, S297F, A456P, and S459F within exons 9, 13, and 14 were detected using a ddPCR, while the mismatch repair (MMR) status was determined by MMR protein IHC and MSI tests. Additionally, we conducted IHC for p53 and L1CAM. Results: The 183 ECs were categorized into four subgroups:POLE-mutated (15.9%), MMR-deficient (29.0%), p53-abnormal (8.7%), and non-specific molecular profile (NSMP, 46.4%). We further subcategorized the NSMP subgroup into NSMP-L1CAMneg (41.5%) and NSMP-L1CAMpos (4.9%), which we refer to as the molecular L1CAM classification. The molecular L1CAM classification was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (p< 0.001, each). Conclusion: Integrating molecular L1CAM classification can enhance risk stratification in early-stage EC, providing valuable prognostic information to guide treatment decisions and improve patient outcomes.POLEddPCR might be a cost-effective and easy-to-perform test as an alternative toPOLENGS.
目的：为提升早期子宫内膜癌（EC）的风险分层能力，本研究采用替代标志物进行分子分型，包括POLE液滴数字聚合酶链反应（ddPCR）及L1CAM免疫组织化学（IHC）。方法：对183例早期EC患者的存档肿瘤组织进行分析。通过ddPCR检测外显子9、13、14内的POLE致病突变（P286R、V411L、S297F、A456P、S459F），同时采用MMR蛋白IHC及MSI检测确定错配修复（MMR）状态。此外，对p53及L1CAM进行IHC检测。结果：183例EC被分为四个亚组：POLE突变型（15.9%）、MMR缺陷型（29.0%）、p53异常型（8.7%）及非特异性分子谱型（NSMP，46.4%）。我们进一步将NSMP亚组细分为NSMP-L1CAM阴性（41.5%）与NSMP-L1CAM阳性（4.9%），并将其定义为分子L1CAM分型。该分型是无复发生存期（RFS）与总生存期（OS）的独立预后因素（均为p<0.001）。结论：整合分子L1CAM分型可优化早期EC的风险分层，为治疗决策提供关键预后信息，从而改善患者结局。POLE ddPCR检测可能是一种经济高效且易于操作的替代方案，可替代POLE二代测序。
肿瘤(癌症)患者之家