Lu Xingmei, Han Qingsong, Li Peng, Huang Kate, Ji Xiuhuan, Chen Suidan, Lin Rixu, Wang Xiaoyu
Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Department of Animal Science, Wenzhou Vocational College of Scienc & Technology, Wenzhou, Zhejiang, 325006, China.
Diagn Pathol. 2025 Feb 13;20(1):18. doi: 10.1186/s13000-025-01607-4.
Extranodal natural killer/T-cell lymphoma (ENKTCL) is strongly associated with Epstein-Barr virus (EBV) infection. A 30-base-pair deletion in latent membrane protein 1 (del-LMP1) represents the most common variant in the EBV genome, but its clinicopathological significance in ENKTCL remains poorly elucidated. Some scholars suggested that the LMP1 protein product carrying the deletion gene reduced immunogenicity, allowed it to escape immune surveillance in immunocompetent hosts and confer a survival advantage. Therefore, simultaneous assessment of del-LMP1 and LMP1 protein expression may provide deeper insights into the potential role of LMP1 in ENKTCL tumorigenesis and progression. This study aimed to investigate the impact of del-LMP1 and LMP1 protein expression on the clinicopathological manifestations and prognosis of ENKTCL patients in Wenzhou.
The clinical and histological characteristics of 42 ENKTCL cases were retrospectively evaluated. Del-LMP1 was detected using a nested polymerase chain reaction and Sanger sequencing, while LMP1 protein expression was assessed via immunohistochemistry. Overall survival (OS) was analyzed.
The LMP1 gene was identified in 37/42 ENKTCL cases, including 2 wild-type (wt-LMP1), 35 del-LMP1 cases. LMP1 protein expression was positive in 21/42 cases. In the control group, the LMP1 gene was detected in 6/10 cases, all of which were del-LMP1, and the LMP1 protein was positive in 4/10 cases. Fisher's exact test revealed no significant differences between the two groups in the LMP1 gene, del-LMP1, or LMP1 protein expression. Additionally, there was no significant correlation between del-LMP1 and LMP1 protein expression and clinical characteristics such as age, gender, or vascular invasion. However, LMP1 protein expression was significantly higher in necrotic tissues (p = 0.030) and younger patients with del-LMP1 (p = 0.004). Survival analysis showed no significant difference in OS between wt-LMP1 and del-LMP1 patients (p = 0.331) or between LMP1-positive and -negative cases (p = 0.592).
In this retrospective cohort, we demonstrated that del-LMP1 might be the predominant variant rather than a phenotype-associated polymorphism in ENKTCL from a molecular epidemiological perspective. Moreover, LMP1 protein expression was associated with necrotic tissue and younger patients with del-LMP1, possibly due to the enhanced pathogenic effect of the mutated LMP1 isolate protein.
结外自然杀伤/T细胞淋巴瘤（ENKTCL）与爱泼斯坦-巴尔病毒（EBV）感染密切相关。潜伏膜蛋白1中的30个碱基对缺失（del-LMP1）是EBV基因组中最常见的变异，但它在ENKTCL中的临床病理意义仍未完全阐明。一些学者认为，携带缺失基因的LMP1蛋白产物降低了免疫原性，使其能够在免疫功能正常的宿主中逃避免疫监视并赋予生存优势。因此，同时评估del-LMP1和LMP1蛋白表达可能会更深入地了解LMP1在ENKTCL肿瘤发生和进展中的潜在作用。本研究旨在探讨del-LMP1和LMP1蛋白表达对温州ENKTCL患者临床病理表现及预后的影响。
回顾性评估42例ENKTCL患者的临床和组织学特征。采用巢式聚合酶链反应和桑格测序检测del-LMP1，通过免疫组织化学评估LMP1蛋白表达。分析总生存期（OS）。
42例ENKTCL患者中37例检测到LMP1基因，其中2例为野生型（wt-LMP1），35例为del-LMP1。42例中有21例LMP1蛋白表达阳性。在对照组中，10例中有6例检测到LMP1基因，均为del-LMP1，10例中有4例LMP1蛋白阳性。Fisher精确检验显示两组在LMP1基因、del-LMP1或LMP1蛋白表达方面无显著差异。此外，del-LMP1和LMP1蛋白表达与年龄、性别或血管侵犯等临床特征之间无显著相关性。然而，坏死组织中LMP1蛋白表达显著更高（p = 0.030），del-LMP1的年轻患者中LMP1蛋白表达也显著更高（p = 0.004）。生存分析显示，wt-LMP1和del-LMP1患者之间的OS无显著差异（p = 0.331），LMP1阳性和阴性病例之间的OS也无显著差异（p = 0.592）。
在这项回顾性队列研究中，我们从分子流行病学角度证明，del-LMP1可能是ENKTCL中的主要变异，而非表型相关的多态性。此外，LMP1蛋白表达与坏死组织及del-LMP1的年轻患者相关，这可能是由于突变的LMP1分离蛋白的致病作用增强所致。
