Expression of Epstein-Barr Virus-Encoded Proteins in Extranodal NK/T-cell Lymphoma, Nasal Type (ENKL): Differences in Biologic and Clinical Behaviors of LMP1-Positive and -Negative ENKL
Expression of Epstein-Barr Virus-Encoded Proteins in Extranodal NK/T-cell Lymphoma, Nasal Type (ENKL): Differences in Biologic and Clinical Behaviors of LMP1-Positive and -Negative ENKL
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DOI：
10.1158/1078-0432.ccr-11-2395
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发表时间：
2012-04-15
影响因子：
11.5
通讯作者：
Komatsu, Norio
中科院分区：
文献类型：
--
作者：
Kanemitsu, Naoko;Isobe, Yasushi;Komatsu, Norio
目的：鼻型结外NK/T细胞淋巴瘤（ENKL）与EB病毒（EBV）密切相关。为了阐明其致病作用，我们研究了EB病毒编码的蛋白质的表达谱，特别是专注于潜伏膜蛋白1（LMP1）。实验设计：免疫组化进行了使用ENKL病例，这是在1996年和2010年之间诊断在我们的机构的临床样本。我们统计学评估LMP 1阳性与临床病理数据之间的相关性，并进一步检查NF-κ B B RelA和Akt在ENKL细胞株中的磷酸化状态。免疫组化检测EBER，但没有EBNA2，在所有情况下。LMP1阳性22例（73.3%），LMP2A阳性12例（40.0%）。LMP1阳性病例倾向于显示局部疾病（P = 0.060，Fisher精确检验）。磷酸化RelA的核定位和磷酸化Akt的检测主要在LMP 1阳性病例中观察到（分别为P = 0.002和P <0.001，Fisher精确检验）。Hank1细胞中LMP1的RNA沉默实验表明，LMP1的表达与RelA和Akt的磷酸化呈正相关。中位随访期为26.7个月（范围，0.2 - 142.3个月），LMP1阳性和阴性病例的2.5年总生存率估计分别为78.3%和12.5（P 0.001，对数秩检验）。结论：LMP1表达与RelA和Akt的磷酸化相关，可能对ENKL的临床结局有有利影响。临床癌症研究; 18（8）; 2164 - 72。(C)2012年AACR。
Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is closely associated with Epstein-Barr virus (EBV). To elucidate its pathogenetic role, we examined the expression profiles of EBV-encoded proteins, especially focusing on latent membrane protein 1 (LMP1).Experimental Design: Immunohistochemistry was carried out using clinical samples from ENKL cases, which were diagnosed between 1996 and 2010 at our institution. We statistically assessed the correlation between LMP1 positivity and the clinicopathologic data and further examined phosphorylation status of NF-kappa B RelA and Akt in ENKL cell lines.Results: Most of the 30 examined cases showed pleomorphic morphology, natural killer cell immunophenotype, and a localized disease. Immunohistochemistry detected EBERs, but not EBNA2, in all cases. LMP1 and LMP2A were positive in 22 (73.3%) and 12 cases (40.0%), respectively. LMP1-positive cases tended to show a localized disease (P = 0.060, the Fisher exact test). Nuclear localization of phosphorylated RelA and detection of phosphorylated Akt were predominantly observed in LMP1-positive cases (P = 0.002 and P < 0.001, respectively, the Fisher exact test). RNA silencing experiments of LMP1 in Hank1 cells suggested a positive correlation between LMP1 expression and phosphorylation of RelA and Akt. With a median follow-up period of 26.7 months (range, 0.2-142.3 months), the 2.5-year overall survival rates for LMP1-positive and -negative cases were estimated at 78.3% and 12.5%, respectively (P 0.001, log-rank test).Conclusions: LMP1 expression shows correlations with phosphorylation of RelA and Akt and possibly has a favorable impact on clinical outcome in ENKL. Clin Cancer Res; 18(8); 2164-72. (C) 2012 AACR.