Morgan Elizabeth A, Sweeney M Patrick, Tomoka Tamiwe, Kopp Nadja, Gusenleitner Daniel, Redd Robert A, Carey Christopher D, Masamba Leo, Kamiza Steve, Pinkus Geraldine S, Neuberg Donna S, Rodig Scott J, Milner Danny A, Weinstock David M
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Tulane University School of Medicine, New Orleans, LA.
Blood Adv. 2016 Nov 22;1(1):84-92. doi: 10.1182/bloodadvances.2016000026. eCollection 2016 Nov 29.
Diagnostics and supportive care for patients with non-Hodgkin lymphoma (NHL) in lower- and middle-income countries (LMICs) are lacking. We hypothesized that high-throughput transcription-based diagnostics could classify NHL specimens from Malawi amenable to targeted therapeutics. We established tissue microarrays and classified 328 cases diagnosed by hematoxylin and eosin as NHL at University of Malawi College of Medicine using immunohistochemistry (IHC) for conventional markers and therapeutic targets. A subset was analyzed using NanoString-based expression profiling with parsimonious transcriptional classifiers. Overall, 72% of lymphomas were high-grade B-cell tumors, subsets of which were enriched for expression of MYC, BCL2, and/or PD-L1. A 21-gene transcriptional classifier, previously validated in Western cohorts, divided 96% of diffuse large B-cell lymphomas (DLBCLs) with 100% of B-cell lymphomas, unclassifiable, into 1 cluster and 88% of Burkitt lymphomas into a separate cluster. Cell-of-origin categorization of 36 DLBCLs by NanoString lymphoma subtyping test (LST) revealed 69% concordance with IHC. All discordant cases were classified as germinal center B cell-like (GCB) by LST but non-GCB by IHC. In summary, utilization of advanced diagnostics facilitates objective assessment and segregation of biologically defined subsets of NHL from an LMIC without expert review, thereby establishing a basis for the implementation of effective and less toxic targeted agents.
低收入和中等收入国家（LMICs）缺乏针对非霍奇金淋巴瘤（NHL）患者的诊断和支持性治疗。我们推测，基于高通量转录的诊断方法可以对来自马拉维的NHL标本进行分类，从而确定适合靶向治疗的病例。我们制作了组织微阵列，并使用免疫组织化学（IHC）检测传统标志物和治疗靶点，对马拉维医学院确诊的328例苏木精和伊红染色诊断为NHL的病例进行分类。使用基于NanoString的表达谱分析和简约转录分类器对一个子集进行了分析。总体而言，72%的淋巴瘤为高级别B细胞肿瘤，其中部分亚群富含MYC、BCL2和/或PD-L1的表达。一个先前在西方队列中得到验证的21基因转录分类器，将96%的弥漫性大B细胞淋巴瘤（DLBCL）以及100%无法分类的B细胞淋巴瘤分为一个簇，88%的伯基特淋巴瘤分为另一个单独的簇。通过NanoString淋巴瘤亚型检测（LST）对36例DLBCL进行细胞起源分类，结果显示与IHC的一致性为69%。所有不一致的病例经LST分类为生发中心B细胞样（GCB），但经IHC分类为非GCB。总之，利用先进的诊断方法有助于在没有专家评审的情况下，对来自低收入和中等收入国家的NHL进行客观评估，并分离出生物学定义的亚群，从而为实施有效且毒性较小的靶向药物奠定基础。
