Immunohistochemical Double-Hit Score Is a Strong Predictor of Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
Immunohistochemical Double-Hit Score Is a Strong Predictor of Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
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DOI：
10.1200/jco.2011.41.4342
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发表时间：
2012-10-01
影响因子：
45.3
通讯作者：
Moller, Michael Boe
中科院分区：
文献类型：
--
作者：
Green, Tina Marie;Young, Ken H.;Moller, Michael Boe
目的大约 5% 的弥漫性大 B 细胞淋巴瘤 (DLBCL) 是双重打击淋巴瘤 (DHL)，伴有 MYC 和 BCL2 易位。 DHL 的特点是结果不佳。我们测试了高表达 MYC 蛋白和 BCL2 蛋白的 DLBCL 是否具有 DHL 的临床特征和不良预后。 患者和方法 采用免疫组织化学方法对 193 例统一接受利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松 (R-CHOP) 治疗的新发 DLBCL 患者的石蜡包埋淋巴瘤样本进行 MYC、BCL2、 CD10、BCL6 和 MUM1/干扰素调节因子 4，以及 MYC 和 BCL2 的荧光原位杂交 (FISH)。结果 FISH 分析在 6% 的患者中发现了 DHL，这些患者的总体生存期较差（OS；P = .002）。根据免疫组织化学 MYC 和 BCL2 表达，对所有 DLBCL 患者进行双重命中评分 (DHS)。 DHS-2 组由 MYC 和 BCL2 蛋白高表达定义，占患者的 29%。 DHS 2 与较低的完全缓解率 (P = .004)、较短的 OS (P < .001) 和较短的无进展生存期 (PFS; P < .001) 显着相关。在控制国际预后指数和细胞来源亚型的多变量模型中，与 OS 和 PFS 保持高度显着相关性（OS，P < .001；PFS，P < .001）。 DHS 在一个由 116 名接受 R-CHOP 治疗的患者组成的独立队列中得到验证。结论免疫组织化学 DHS 定义了具有双重打击生物学特性的 DLBCL 的一个大子集，并且与 R-CHOP 治疗患者的不良预后密切相关。 J 临床肿瘤杂志 30：3460-3467。 (C) 2012 年美国临床肿瘤学会
PurposeApproximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs.Patients and MethodsParaffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2.ResultsFISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP.ConclusionThe immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP. J Clin Oncol 30:3460-3467. (C) 2012 by American Society of Clinical Oncology