Keegan Theresa H M, Glaser Sally L, Clarke Christina A, Gulley Margaret L, Craig Fiona E, Digiuseppe Joseph A, Dorfman Ronald F, Mann Risa B, Ambinder Richard F
Northern California Cancer Center, 2201 Walnut Ave, Ste 300, Fremont, CA 94538-2334, USA.
J Clin Oncol. 2005 Oct 20;23(30):7604-13. doi: 10.1200/JCO.2005.02.6310. Epub 2005 Sep 26.
Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype.
Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models.
In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3).
In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.
霍奇金淋巴瘤（HL）细胞中的爱泼斯坦-巴尔病毒（EBV）被认为是这种异质性疾病的一种预后标志物，但研究结果不一，这可能是由于所选患者系列以及未认识到年龄对预后的影响。本研究在一个基于人群的队列中评估了HL后的生存情况，该队列规模足够大，能够检验EBV与其他因素（包括年龄、性别和组织学亚型）的联合作用。
纳入了1988年年中至1997年期间在旧金山湾区确诊的922例经典HL患者，其存档的活检标本通过免疫组织化学和原位杂交检测EBV。通过2003年12月30日随访生命状态（中位随访时间为97个月）。采用Kaplan-Meier法和Cox比例风险回归模型分析总生存和疾病特异性生存。
在15岁以下儿童中，EBV的存在与良好生存有提示性关联（P = 0.07）。在15至44岁的成年人中，EBV虽提示有保护作用，但不影响HL的预后。在老年人（45至96岁）中，EBV的存在使总死亡和HL特异性死亡风险几乎增加一倍，但仅针对结节硬化（NS）组织学亚型的患者（死亡风险比 = 2.5；95% CI，1.5至4.3）。
在HL中，EBV肿瘤细胞的存在与年轻患者更好的生存以及老年NS患者较差的生存相关，独立于其他因素。年龄和组织学导致的预后差异可能表明存在生物学上不同的疾病实体。EBV是一个有意义的预后标志物的证据可能具有治疗相关性。
