Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significance
Abstract Background 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 ENK...
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BMC
2025-02-01
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| Series: | Diagnostic Pathology |
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| Online Access: | https://doi.org/10.1186/s13000-025-01607-4 |
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| author | Xingmei Lu Qingsong Han Peng Li Kate Huang Xiuhuan Ji Suidan Chen Rixu Lin Xiaoyu Wang |
| author_facet | Xingmei Lu Qingsong Han Peng Li Kate Huang Xiuhuan Ji Suidan Chen Rixu Lin Xiaoyu Wang |
| author_sort | Xingmei Lu |
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| description | Abstract Background 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. Methods 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. Results 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). Conclusion 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. |
| format | Article |
| id | doaj-art-656a2b87b09e4c839db301a62dd20b9b |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-656a2b87b09e4c839db301a62dd20b9b2025-08-20T02:48:29ZengBMCDiagnostic Pathology1746-15962025-02-0120111010.1186/s13000-025-01607-4Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significanceXingmei Lu0Qingsong Han1Peng Li2Kate Huang3Xiuhuan Ji4Suidan Chen5Rixu Lin6Xiaoyu Wang7Department of Pathology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Animal Science, Wenzhou Vocational College of Scienc & TechnologyDepartment of Pathology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pathology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pathology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pathology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pathology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pathology, the First Affiliated Hospital of Wenzhou Medical UniversityAbstract Background 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. Methods 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. Results 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). Conclusion 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.https://doi.org/10.1186/s13000-025-01607-4Extranodal natural killer/T-cell lymphoma (ENKTCL)Latent membrane protein 1 (LMP1)Epstein-Barr virus (EBV) |
| spellingShingle | Xingmei Lu Qingsong Han Peng Li Kate Huang Xiuhuan Ji Suidan Chen Rixu Lin Xiaoyu Wang Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significance Diagnostic Pathology Extranodal natural killer/T-cell lymphoma (ENKTCL) Latent membrane protein 1 (LMP1) Epstein-Barr virus (EBV) |
| title | Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significance |
| title_full | Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significance |
| title_fullStr | Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significance |
| title_full_unstemmed | Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significance |
| title_short | Detection of the 30-bp deletion and protein expression of Epstein-Barr virus latent membrane protein 1 in extranodal NK/T cell lymphoma and its clinicopathological significance |
| title_sort | detection of the 30 bp deletion and protein expression of epstein barr virus latent membrane protein 1 in extranodal nk t cell lymphoma and its clinicopathological significance |
| topic | Extranodal natural killer/T-cell lymphoma (ENKTCL) Latent membrane protein 1 (LMP1) Epstein-Barr virus (EBV) |
| url | https://doi.org/10.1186/s13000-025-01607-4 |
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