Ishii Hideyuki, Ogino Takeshi, Berger Christoph, Köchli-Schmitz Nicole, Nagato Toshihiro, Takahara Miki, Nadal David, Harabuchi Yasuaki
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan.
J Med Virol. 2007 May;79(5):562-72. doi: 10.1002/jmv.20853.
Quantitative real-time polymerase chain reaction (PCR) was utilized to measure serum EBV DNA levels of BamHI W fragment and latent membrane protein 1 (LMP1) in 20 nasal natural killer (NK)/T-cell lymphoma patients. Both serum EBV DNAs were detected at high levels in all patients, but the levels were below the limit of detection in all healthy controls. The BamHI Z fragment, Epstein-Barr-replication activator (ZEBRA) expression was detected in a small proportion (0.1-3%) of lymphoma cells from 10 (50%) of the patients. Patients with ZEBRA expression showed significantly higher DNA levels of BamHI W and LMP1 (P = 0.0081, P = 0.004), suggesting that EBV DNA may be caused by EBV replication from lymphoma cells. Kaplan-Meier and univariate analyses revealed that high DNA levels of BamHI W and LMP1 at pre-treatment and high BamHI W DNA level at post-treatment were associated with short disease-free survival and overall survival (P < 0.05, each). Although the DNA levels of BamHI W and LMP1 correlated significantly, their dynamics were not always parallel. Patients with low pre-treatment level of both EBV DNAs showed a favorable course, in contrast to patients with high pre-treatment level of both EBV DNAs who showed an aggressive course (P = 0.0085). More importantly, the high pre-treatment level of both EBV DNAs was determined as the only independent prognostic factor among various prognostic factors. These data suggest that simultaneous measurement of serum levels of both BamHI W and LMP1 DNAs may be useful for diagnosis, disease monitoring, and prediction of prognosis for nasal NK/T-cell lymphoma patients.
采用定量实时聚合酶链反应（PCR）检测了20例鼻型自然杀伤（NK）/T细胞淋巴瘤患者血清中EBV BamHI W片段和潜伏膜蛋白1（LMP1）的DNA水平。所有患者血清中均检测到高水平的EBV DNA，但在所有健康对照中均低于检测限。在10例（50%）患者的小部分（0.1 - 3%）淋巴瘤细胞中检测到了BamHI Z片段、爱泼斯坦-巴尔病毒复制激活因子（ZEBRA）表达。ZEBRA表达阳性的患者BamHI W和LMP1的DNA水平显著更高（P = 0.0081，P = 0.004），提示EBV DNA可能由淋巴瘤细胞中的EBV复制所致。Kaplan-Meier分析和单因素分析显示，治疗前BamHI W和LMP1的高DNA水平以及治疗后BamHI W的高DNA水平与无病生存期和总生存期缩短相关（均P < 0.05）。尽管BamHI W和LMP1的DNA水平显著相关，但其动态变化并不总是平行的。治疗前两种EBV DNA水平均低的患者病程良好，而治疗前两种EBV DNA水平均高的患者病程侵袭性强（P = 0.0085）。更重要的是，治疗前两种EBV DNA的高水平被确定为各种预后因素中唯一的独立预后因素。这些数据表明，同时检测血清中BamHI W和LMP1 DNA水平可能有助于鼻型NK/T细胞淋巴瘤患者的诊断、病情监测和预后预测。
