Valea Cristian-Viktor, Klein Maurice, Hallermann Christian, Schulze Hans-Joachim, Raguse Jan-Dirk, Wermker Kai
AllDent Zahnzentrum Leipzig GmbH, Leipzig, Germany.
Department of Oral and Maxillofacial Surgery, School of Medicine, University Hospital RWTH Aachen, Aachen, Germany.
Front Oncol. 2025 Mar 11;14:1438021. doi: 10.3389/fonc.2024.1438021. eCollection 2024.
Enhancer of zeste homolog 2 (EZH2) is a transcriptional enzyme implicated in tumor development and is often correlated to poor patient outcomes in various malignancies. The study evaluated various methods for EZH2 expression in lip and ear squamous cell carcinomas (LSCC, ESCC) by matching patients with and without lymph node metastasis (LNM) and further analysis of clinical outcome parameters. EZH2 inhibition therapy has shown promising results in multiple cancer entities, with ongoing research exploring its potential in other malignancies. This approach may also be applicable to high-risk LSCC and ESCC.
A total of 122 patients who had been surgically treated for LSCC and ESCC were selected to form LNM-positive and LNM-negative matched pairs. EZH2 expression has been examined after immunostaining of the tumor tissue with EZH2-antibodies and quantified as extent, intensity, and score. Pursuing the clinical benefit, we analyzed three different EZH2-score approaches to determine aberrations in EZH2 expression.
While the overall EZH2 extent did not correlate with clinical outcome, the EZH2-intensity and -score was lower in patients who developed a local relapse or distant metastasis (DM). High EZH2-scores correlated with increasing grading, pN-, and American Joint Committee on Cancer-stage. Overall, the carcinoma tissue samples showed a high expression of EZH2 (mean expression > 60%).
The hypothesis of the predictive prognostic contribution of EZH2 in clinical decisions regarding the occurrence of LNM was not substantiated by our data. Nevertheless, the elevated expression of EZH2 we have observed in our findings could be utilized as a pretherapeutic assessment prior to targeted therapies with tazemetostat. Subsequent research should substantiate this hypothesis.
zeste 同源物 2 增强子（EZH2）是一种与肿瘤发展相关的转录酶，在各种恶性肿瘤中常与患者的不良预后相关。本研究通过匹配有和无淋巴结转移（LNM）的唇和耳鳞状细胞癌（LSCC、ESCC）患者，评估了 EZH2 在其中表达的各种方法，并进一步分析了临床结局参数。EZH2 抑制疗法在多种癌症实体中已显示出有前景的结果，目前正在进行的研究探索其在其他恶性肿瘤中的潜力。这种方法也可能适用于高危 LSCC 和 ESCC。
总共选择了 122 例接受过 LSCC 和 ESCC 手术治疗的患者，形成 LNM 阳性和 LNM 阴性匹配对。用 EZH2 抗体对肿瘤组织进行免疫染色后检测 EZH2 表达，并将其量化为范围、强度和评分。为了追求临床益处，我们分析了三种不同的 EZH2 评分方法以确定 EZH2 表达的异常情况。
虽然 EZH2 的总体范围与临床结局无关，但发生局部复发或远处转移（DM）的患者中 EZH2 强度和评分较低。高 EZH2 评分与分级增加、pN-和美国癌症联合委员会分期相关。总体而言，癌组织样本显示 EZH2 高表达（平均表达>60%）。
我们的数据并未证实 EZH2 在关于 LNM 发生的临床决策中具有预测预后作用的假设。然而，我们在研究中观察到的 EZH2 表达升高可作为使用他泽司他进行靶向治疗前的治疗前评估。后续研究应证实这一假设。
