Merkel cell carcinoma (MCC) is an aggressive skin tumor with neuroendocrine differentiation, mainly affecting elderly population or immunocompromised individuals. As methylation of the human telomerase reverse transcriptase (mhTERT) has been shown to be a prognostic factor in different tumors, we investigated its role in MCC, in particular in intron 4–5 where rs10069690 has been mapped and recognized as a cancer susceptibility locus. DNA methylation analysis of hTERT gene was assessed retrospectively in a cohort of 69 MCC patients from the University of Bologna, University of Turin and University of Insubria. Overall mortality was evaluated with Kaplan-Meier curves and multivariable Royston-Parmar models. High levels of mhTERT (mhTERT_high) (HR = 2.500, p = 0.015) and p63 (HR = 2.659, p = 0.016) were the only two clinico-pathological features significantly associated with a higher overall mortality at the multivariate analysis. We did not find different levels of mhTERT between MCPyV (+) and (−) cases (21 vs 14, p = 0.554); furthermore, mhTERT_high was strongly associated with older age (80.5 vs 72 years, p = 0.026), no angioinvasion (40.7% vs 71.0%, p = 0.015), lower Ki67 (50 vs 70%, p = 0.005), and PD-L1 expressions in both tumor (0 vs 3%, p = 0.021) and immune cells (0 vs 10%, p = 0.002). mhTERT is a frequently involved epigenetic mechanism and a relevant prognostic factor in MCC. In addition, it belongs to the shared oncogenic pathways of MCC (MCPyV and UV-radiations) and it could be crucial, together with other epigenetic and genetic mechanisms as gene amplification, in determining the final levels of hTERT mRNA and telomerase activity in these patients.

默克尔细胞癌 (MCC) 是一种具有神经内分泌分化的侵袭性皮肤肿瘤，主要影响老年人群或免疫功能低下的个体。由于人类端粒酶逆转录酶 (m hTERT ) 的甲基化已被证明是不同肿瘤中的预后因素，我们研究了它在 MCC 中的作用，特别是在内含子 4-5 中，其中 rs10069690 已被定位并被识别为癌症易感基因座. hTERT基因的 DNA 甲基化分析在来自博洛尼亚大学、都灵大学和因苏布里亚大学的 69 名 MCC 患者队列中进行了回顾性评估。使用 Kaplan-Meier 曲线和多变量 Royston-Parmar 模型评估总体死亡率。高水平的 m hTERT (m hTERT_高）（HR = 2.500，p  =  0.015）和 p63（HR = 2.659，p  =  0.016）是在多变量分析中与较高的总体死亡率显着相关的仅有的两个临床病理学特征。我们没有发现MCPyV (+) 和 (-) 病例之间的 m hTERT水平不同（21 对 14， p  =  0.554）；此外，m hTERT_高与年龄较大（80.5 对 72 岁，p  =  0.026）、无血管浸润（40.7% 对 71.0%，p  =  0.015）、Ki67 较低（50 对 70%，p  =  0.005 ）密切相关) 和 PD-L1 在肿瘤 (0 vs 3%, p  =  0.021 ) 和免疫细胞 (0 vs 10%, p  =  0.002 ) 中的表达。m hTERT是 MCC 中经常涉及的表观遗传机制和相关的预后因素。此外，它属于 MCC（MCPyV 和紫外线辐射）的共同致癌途径，与其他表观遗传和遗传机制（如基因扩增）一起，在确定这些患者的hTERT mRNA 和端粒酶活性的最终水平方面可能是至关重要的.