Multidisciplinary Head and Neck Cancer Center, National Institute of Oncology, H-1122 Budapest, Hungary.
Center of Tumor Pathology, National Institute of Oncology, H-1122 Budapest, Hungary.
Int J Mol Sci. 2024 May 11;25(10):5250. doi: 10.3390/ijms25105250.
EZH2 (Enhancer of zeste homolog 2) promotes tumor growth and survival through numerous mechanisms and is a promising target for novel therapeutic approaches. We aimed to characterize the expression of EZH2 in the tumors of young head-and-neck squamous cell cancer (HNSCC) patients in comparison with the general HNSCC patient population. We used formalin-fixed, paraffin-embedded tissue blocks from 68 random young HNSCC patients (≤39 years, median age: 36 years; diagnosed between 2000 and 2018), which were compared with the samples of 58 age- and gender-matched general HNSCC subjects (median age: 62 years; all diagnosed in the year 2014). EZH2 and p53 expression of the tumors was detected using immunohistochemical staining. Lower EZH2 expression was found to be characteristic of the tumors of young HNSCC patients as opposed to the general population (median EZH2 staining intensity: 1 vs. 1.5 respectively, < 0.001; median fraction of EZH2 positive tumor cells: 40% vs. 60%, respectively, = 0.003, Mann-Whitney). Cox analysis identified a more advanced T status (T3-4 vs. T1-2), a positive nodal status, and alcohol consumption, but neither intratumoral EZH2 nor p53 were identified as predictors of mortality in the young patient group. The lower EZH2 expression of young HNSCC patients' tumors discourages speculations of a more malignant phenotype of early-onset tumors and suggests the dominant role of patient characteristics. Furthermore, our results might indicate the possibility of an altered efficacy of the novel anti-EZH2 therapies in this patient subgroup.
EZH2（增强子结合锌指蛋白 2）通过多种机制促进肿瘤生长和存活，是新型治疗方法的有前途的靶点。我们旨在比较年轻头颈部鳞状细胞癌（HNSCC）患者肿瘤中 EZH2 的表达与一般 HNSCC 患者群体。我们使用了来自 68 名随机年轻 HNSCC 患者（≤39 岁，中位年龄：36 岁；诊断时间为 2000 年至 2018 年）的福尔马林固定、石蜡包埋组织块，并与 58 名年龄和性别匹配的一般 HNSCC 患者（中位年龄：62 岁；所有患者均在 2014 年诊断）的样本进行了比较。使用免疫组织化学染色检测肿瘤中的 EZH2 和 p53 表达。与一般人群相比，年轻 HNSCC 患者的肿瘤中 EZH2 表达较低（中位数 EZH2 染色强度：1 与 1.5， < 0.001；EZH2 阳性肿瘤细胞的中位数比例：40%与 60%，分别， = 0.003，Mann-Whitney）。Cox 分析确定了更晚期的 T 分期（T3-4 与 T1-2）、阳性淋巴结状态和饮酒，但年轻患者组中，肿瘤内 EZH2 或 p53 均未被确定为死亡的预测因子。年轻 HNSCC 患者肿瘤中较低的 EZH2 表达阻止了对早期发病肿瘤恶性表型的推测，并表明了患者特征的主导作用。此外，我们的结果可能表明，新型抗 EZH2 治疗在该患者亚组中的疗效可能发生改变。
