Nyman Heidi, Jerkeman Mats, Karjalainen-Lindsberg Marja-Liisa, Banham Alison H, Leppä Sirpa
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Mod Pathol. 2009 Aug;22(8):1094-101. doi: 10.1038/modpathol.2009.73. Epub 2009 May 15.
Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high- and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell lymphoma patients treated uniformly with R-CHOP. When the modified classification using MUM1/IRF4 and FOXP1 positivities as activated B-cell-like markers was applied to distinguish the patients between the activated B-cell-like and other diffuse large B-cell lymphoma subtypes, a significantly worse outcome was seen for the patients with the activated B-cell-like phenotype (3-year failure-free survival 63 vs 82%, P=0.048, overall survival 69 vs 85%, P=0.110). Similarly, according to the Muris algorithm, the group 2 patients representing Bcl-2-positive post-germinal center patients showed an inferior outcome in comparison to the group 1 patients (failure-free survival 59 vs 81%, P=0.041, overall survival 67 vs 82%, P=0.159). In contrast, when the classification of the same cohort was performed according to the Hans algorithm, no significant difference in survival was observed between the germinal center and non-germinal center patients. In conclusion, the data suggest that both the modified activated B-cell-like and Muris classifications define the non-germinal center phenotype as an adverse risk factor in R-CHOP-treated diffuse large B-cell lymphoma patients.
基因表达谱研究最初使得弥漫性大B细胞淋巴瘤能够被分为生发中心型和活化B细胞样亚型，这两种亚型在接受化疗时可界定高危和低危患者群体。然而，试图通过免疫组织化学方法重现这种预后分类的研究结果并不一致。本研究的目的是确定聚焦于活化B细胞样标志物的改良细胞起源免疫组织化学分类是否可用于预测接受免疫化疗的弥漫性大B细胞淋巴瘤患者的预后。对88例接受R-CHOP方案统一治疗的弥漫性大B细胞淋巴瘤患者的样本进行免疫组织化学检测，以确定CD10、Bcl-6、MUM1/IRF4、Bcl-2和FOXP1的表达情况。当采用以MUM1/IRF4和FOXP1阳性作为活化B细胞样标志物的改良分类方法来区分活化B细胞样亚型和其他弥漫性大B细胞淋巴瘤亚型的患者时，活化B细胞样表型的患者预后明显更差（3年无失败生存率分别为63%和82%，P=0.048；总生存率分别为69%和85%，P=0.110）。同样，根据穆里斯算法，代表生发中心后Bcl-2阳性的2组患者与1组患者相比预后较差（无失败生存率分别为59%和81%，P=0.041；总生存率分别为67%和82%，P=0.159）。相比之下，当根据汉斯算法对同一队列进行分类时，生发中心型和非生发中心型患者之间未观察到生存方面的显著差异。总之，数据表明改良的活化B细胞样分类和穆里斯分类均将非生发中心表型定义为接受R-CHOP治疗弥漫性大B细胞淋巴瘤患者的不良风险因素。
