Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies
Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies
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DOI：
10.1200/jco.2014.60.2383
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发表时间：
2015-09-10
影响因子：
45.3
通讯作者：
Gascoyne, Randy D.
中科院分区：
文献类型：
--
作者：
Scott, David W.;Mottok, Anja;Gascoyne, Randy D.
目的为了评估使用最近描述的基于基因表达的 Lymph2Cx 测定法分配的细胞源 (COO) 亚组的预后影响，并与国际预后指数 (IPI) 评分和 MYC/BCL2 共表达状态（双表达者）进行比较。患者和方法使用 Lymph2Cx 测定法进行 COO 分配的重现性通过重复采样进行测试 肿瘤活检和试剂批次的变化。然后将该测定应用于不列颠哥伦比亚省癌症机构使用利妥昔单抗加环磷酰胺、阿霉素、长春新碱和泼尼松 (R-CHOP) 统一治疗的 344 名新发弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者的治疗前福尔马林固定石蜡包埋组织 (FFPET) 活检。使用组织微阵列上的免疫组织化学评估 MYC 和 BCL2 蛋白表达。结果 Lymph2Cx 检测在 49 个重复采样的肿瘤活检样本中的 96% 以及跨试剂批次测试的 83 个 FFPET 活检样本中的 100% 提供了一致的 COO 识别。重要的是，没有观察到明显的错误分类（激活的 B 细胞样 DLBCL 到生发中心 B 细胞样 DLBCL，反之亦然）。与生发中心 B 细胞样 DLBCL 患者相比，活化 B 细胞样 DLBCL 患者的预后显着较差（进展时间、无进展生存期、疾病特异性生存期和总生存期的对数秩 P < 0.001）。在成对多变量分析中，COO 与独立于 IPI 评分和 MYC/BCL2 免疫组织化学的结果相关。 COO 的预后意义在具有中等 IPI 评分的患者和非 MYC 阳性/BCL2 阳性亚组中尤其明显（进展时间的对数秩 P < .001）。 结论 使用 FFPET 活检通过 Lymph2Cx 检测对 DLBCL COO 进行分配，确定了 R-CHOP 后具有显着不同结果的患者组，与 IPI 评分和 MYC/BCL2双重表达。 (C) 2015 年美国临床肿瘤学会
PurposeTo evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression-based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers).Patients and MethodsReproducibility of COO assignment using the Lymph2Cx assay was tested employing repeated sampling within tumor biopsies and changes in reagent lots. The assay was then applied to pretreatment formalin-fixed paraffin-embedded tissue (FFPET) biopsies from 344 patients with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays.ResultsThe Lymph2Cx assay provided concordant COO calls in 96% of 49 repeatedly sampled tumor biopsies and in 100% of 83 FFPET biopsies tested across reagent lots. Critically, no frank misclassification (activated B-cell-like DLBCL to germinal center B-cell-like DLBCL or vice versa) was observed. Patients with activated B-cell-like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell-like DLBCL (log-rank P < .001 for time to progression, progression-free survival, disease-specific survival, and overall survival). In pairwise multivariable analyses, COO was associated with outcomes independent of IPI score and MYC/BCL2 immunohistochemistry. The prognostic significance of COO was particularly evident in patients with intermediate IPI scores and the non-MYC-positive/BCL2-positive subgroup (log-rank P < .001 for time to progression).ConclusionAssignment of DLBCL COO by the Lymph2Cx assay using FFPET biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression. (C) 2015 by American Society of Clinical Oncology