Ichiki Akifumi, Carreras Joaquim, Miyaoka Masashi, Kikuti Yara Yukie, Jibiki Tadashi, Tazume Kei, Watanabe Shigeki, Sasao Tamotsu, Obayashi Yoshiaki, Onizuka Makoto, Ohmachi Ken, Yoshiba Fumiaki, Shirasugi Yukari, Ogawa Yoshiaki, Kawada Hiroshi, Nakamura Naoya, Ando Kiyoshi
Department of Hematology and Oncology, Tokai University, School of Medicine.
Department of Pathology, Tokai University, School of Medicine.
J Clin Exp Hematop. 2017;57(2):54-63. doi: 10.3960/jslrt.17029.
The estimation of clinical prognosis for diffuse large B-cell lymphoma (DLBCL) with a quick, cost-efficient method is necessary because of the clinical heterogeneity of this disease, which leads to death, relapsed or refractory disease in approximately 40% of patients. We analyzed 320 cases diagnosed from 2007 to 2013 treated with R-CHOP therapy at Tokai University Hospital and associated institutions. DLBCL was classified according to the cell-of-origin using the Hans algorithm [germinal center B-cell-like (GCB) vs non-GCB subtypes], and into 6 subgroups derived from combinations of CD10, BCL6 and MUM1 markers. The percentage of GCB and non-GCB (NGCB) subtypes was 35% and 65%, respectively. GCB-DLBCL was characterized by lower BCL2 immunohistochemical expression, extranodal sites ＜1, better therapeutic response, and favorable overall survival (OS) and progression free survival (PFS) (P＜0.01). The most frequent subgroup was NGCB-1 (CD10BCL6MUM1, 51%) followed by GCB-1 (CD10BCL6MUM1, 21%), NGCB-2 (CD10BCL6MUM1, 13%), GCB-2 (CD10BCL6MUM1, 10%), GCB-3 (CD10BCL6MUM1, 4%) and NGCB-3 (CD10BCL6MUM1, 2%). In comparison with GCB-2 and GCB-3 (both MUM1), the GCB-1 (MUM1) was characterized by favorable PFS (5-year PFS 84% vs 65%, OR 0.368, P＜0.05), independent of high LDH (associated with unfavorable PFS, OR 7.04, P＜0.01) in the multivariate analysis. This predictive value of MUM1 was independent of CD10. Interestingly, triple-negative NGCB-3 tended to have a more favorable prognosis than the other NGCB subgroups. In conclusion, the Hans classifier is a valid method to evaluate the prognosis of DLBCL NOS. In the GCB subtypes, GCB subtypes, MUM1-positivity is associated with a more favorable outcome (PFS).
由于弥漫性大B细胞淋巴瘤（DLBCL）具有临床异质性，约40%的患者会出现死亡、复发或难治性疾病，因此需要一种快速、经济高效的方法来评估其临床预后。我们分析了2007年至2013年在东海大学医院及相关机构接受R-CHOP治疗的320例确诊病例。DLBCL根据起源细胞使用Hans算法进行分类[生发中心B细胞样（GCB）与非GCB亚型]，并分为由CD10、BCL6和MUM1标记物组合衍生的6个亚组。GCB和非GCB（NGCB）亚型的百分比分别为35%和65%。GCB-DLBCL的特征是BCL2免疫组化表达较低、结外部位＜1、治疗反应较好以及总生存期（OS）和无进展生存期（PFS）良好（P＜0.01）。最常见的亚组是NGCB-1（CD10BCL6MUM1，51%），其次是GCB-1（CD10BCL6MUM1，21%）、NGCB-2（CD10BCL6MUM1，13%）、GCB-2（CD10BCL6MUM1，10%）、GCB-3（CD10BCL6MUM1，4%）和NGCB-3（CD10BCL6MUM1，2%）。与GCB-2和GCB-3（均为MUM1）相比，GCB-1（MUM1）的特征是PFS良好（5年PFS为84%对65%，OR 0.368，P＜0.05），在多变量分析中与高乳酸脱氢酶（与不良PFS相关，OR 7.04，P＜0.01）无关。MUM1的这种预测价值与CD10无关。有趣的是，三阴性NGCB-3的预后往往比其他NGCB亚组更有利。总之，Hans分类器是评估DLBCL NOS预后的有效方法。在GCB亚型中，GCB亚型中MUM1阳性与更有利的结局（PFS）相关。
