Anderson John J, Fordham Sarah, Overman Lynne, Dignum Helen, Wood Katrina, Proctor Stephen J, Crosier Stephen, Angus Brian, Culpin Rachel E, Mainou-Fowler Tryfonia
Department of Academic Haematology, Northern Institute for Cancer Research, The University of Newcastle, Newcastle-upon-Tyne, NE2 4HH, UK.
Int J Oncol. 2009 Nov;35(5):961-71. doi: 10.3892/ijo_00000409.
Diffuse large B-cell lymphoma (DLBCL) forms a heterogeneous collection of aggressive non-Hodgkin's Lymphoma in which three principle classes of neoplasia have been defined according to gene expression and immunophenotyping studies. The present investigation sought to examine the immunophenotype of proposed subgroups and relate these to patient survival. A series of 155 DLBCL treated uniformly with anthracycline therapy in clinical trials, were stratified upon the basis of common biomarker expression with combination immunophenotype being related to patient overall survival. Stratification of tumours with respect to combined expression profiles of the three biological markers (CD10, Bcl-6 and MUM-1) revealed six groups showing significant differences in survival (p=0.014). The greatest difference resided between distinct populations of germinal centre (GC) cell tumours; the first being CD10-, Bcl-6+, MUM-1- and the second CD10+ Bcl-6+ MUM-1+ (p=0.002). The former group displayed median survival time of 143 months, the latter only 11 months. A third population of GC tumours (CD10+ Bcl-6+ and MUM-1-) also displayed a relative short median survival (32 months). Of the three groups presenting a non-GC or activated B cell (NGC/ABC) phenotype, only one (CD10-, Bcl-6+ and MUM-1+) presented short-term median survival (27 months) comparable with poor prognosis GC sub-populations. Within the remaining ABC tumour groups (CD10- Bcl-6- MUM-1- and CD10- Bcl-6- MUM-1+) patients presented intermediate median survival times of 54 and 58 months, respectively. Thus, the GC phenotype did not act as a universal indicator of good clinical prognosis, but rather multiple groups of GC tumours were associated with distinct overall survival profiles. Ultimately, the data allowed definition of a predictive algorithm defining three groups predicting poor, intermediate and good clinical prognosis. The first of these comprised two patient sub-populations with GC-like tumours together with one sub-population of NGC/ABC, the second two sub-populations of ABC-like tumours, and the final a single group of GC-like tumours associated with optimal long-term survival.
弥漫性大B细胞淋巴瘤（DLBCL）是侵袭性非霍奇金淋巴瘤的异质性集合，根据基因表达和免疫表型研究已定义了三种主要的肿瘤类型。本研究旨在检查所提议亚组的免疫表型，并将其与患者生存率相关联。在临床试验中，对155例接受蒽环类药物统一治疗的DLBCL患者进行了研究，根据常见生物标志物表达进行分层，并将联合免疫表型与患者总生存率相关联。根据三种生物标志物（CD10、Bcl-6和MUM-1）的联合表达谱对肿瘤进行分层，发现有六个组的生存率存在显著差异（p = 0.014）。生发中心（GC）细胞肿瘤的不同群体之间差异最大；第一组为CD10-、Bcl-6+、MUM-1-，第二组为CD10+、Bcl-6+、MUM-1+（p = 0.002）。前一组的中位生存时间为143个月，后一组仅为11个月。第三组GC肿瘤（CD10+、Bcl-6+和MUM-1-）的中位生存期也相对较短（32个月）。在呈现非GC或活化B细胞（NGC/ABC）表型的三组中，只有一组（CD10-、Bcl-6+和MUM-1+）的短期中位生存期（27个月）与预后不良的GC亚群相当。在其余的ABC肿瘤组（CD10-、Bcl-6-、MUM-1-和CD10-、Bcl-6-、MUM-1+）中，患者的中位生存时间分别为54个月和58个月，处于中等水平。因此，GC表型并非良好临床预后的普遍指标，而是多组GC肿瘤与不同的总生存情况相关。最终，这些数据允许定义一种预测算法，该算法定义了预测临床预后不良、中等和良好的三组。其中第一组包括两个具有GC样肿瘤的患者亚群以及一个NGC/ABC亚群，第二组包括两个ABC样肿瘤亚群，最后一组是与最佳长期生存相关的单一GC样肿瘤组。
