Epstein-Barr virus infection and expression of B-cell oncogenic markers in HIV-related diffuse large B-cell Lymphoma.
Epstein-Barr virus infection and expression of B-cell oncogenic markers in HIV-related diffuse large B-cell Lymphoma.
复制标题
DOI：
10.1158/1078-0432.ccr-11-3169
复制
发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Said J
中科院分区：
文献类型：
--
作者：
Chao C;Silverberg MJ;Martínez-Maza O;Chi M;Abrams DI;Haque R;Zha HD;McGuire M;Xu L;Said J
EB病毒（EBV）介导的淋巴瘤发生在艾滋病毒感染的背景下已被广泛接受。然而，人们对EBV如何影响预后知之甚少。我们研究了HIV相关弥漫性大B细胞淋巴瘤（DLBCL）中EBV感染与特异性B细胞致癌标记物表达相关的假设，并检查了检测EBV感染的预后效用。确定了1996-2007年间在Kaiser Permanente加州诊断的HIV相关DLBCL病例。免疫组织化学染色用于分析所选标记物的表达，所述标记物是细胞周期调节剂、B细胞激活剂和抗凋亡蛋白等。EBV感染通过EBV RNA原位杂交确定。使用斯皮尔曼相关系数检验EBV和标记物表达之间的相关性。在多变量考克斯模型中检查EBV状态的预后效用，该模型调整了国际预后指数（IPI）。受试者工作特征（ROC）分析用于评估模型辨别力的改善。纳入70例HIV相关DLBCL病例（31% EBV+）。EBV+肿瘤与BLIMP 1和CD 30的表达增加以及BCL 6和LMO 2的表达减少相关。EBV+肿瘤与2年总死亡率升高独立相关[风险比=3.3（95% CI：1.6-6.6）]。当在预测模型中结合肿瘤EBV状态和IPI时，ROC曲线下面积显示出改善的模型区分度[0.65 vs. 0.74（仅IPI）]。我们的研究结果表明，EBV感染与参与NF-κB通路的几种肿瘤标志物的表达相关，检测肿瘤EBV状态可能对HIV相关DLBCL的预后有用。
Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL), and examined the prognostic utility of detecting EBV infection. HIV-related DLBCL cases diagnosed between 1996–2007 within Kaiser Permanente California were identified. Immunohistochemistry staining was used to analyze the expression of selected markers that are cell cycle regulators, B-cell activators, and anti-apoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman’s correlation coefficient. The prognostic utility of EBV status was examined in multivariable Cox model adjusting for international prognostic index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination. Seventy HIV-related DLBCL cases were included (31% EBV+). EBV+ tumor was associated with increased expression of BLIMP1 and CD30, and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [hazard ratio=3.3 (95% CI: 1.6–6.6)]. Area under the ROC curve demonstrated improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)]. Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway, and that detecting tumor EBV status may have prognostic utility in HIV-related DLBCL.