Pathology, CHU Dijon, Dijon.
Pathology, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil, Créteil and IMRB, INSERM U955 Unité, Créteil.
Ann Oncol. 2017 May 1;28(5):1042-1049. doi: 10.1093/annonc/mdx022.
Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial.
We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples.
The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81).
Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival.
NCT00144755.
我们的目的是评估在接受利妥昔单抗、环磷酰胺、盐酸多柔比星、长春新碱和泼尼松（R-CHOP）治疗的老年患者中，由 Hans 算法定义的细胞起源（COO）和 MYC/BCL2 共表达这两个主要生物学危险因素是否保持其在大型前瞻性临床试验中的预后价值。
我们评估了 285 例石蜡包埋样本，这些样本来自参加 Lymphoma Study Association 试验 LNH03-6B 的患者（年龄 60-80 岁），这些患者接受了 R-CHOP 治疗。我们在 62 例有可用冷冻组织样本的肿瘤亚组中，将根据 Wright 算法定义的转录组 COO 与根据 Hans 算法定义的 COO 进行了相关性分析。
根据 Hans 算法定义的非生发中心 B 细胞样表型和 BCL2 表达（但不是 MYC 和 BCL2 共表达）预测无进展生存期（HR=1.78，P=0.003 和 HR=1.79，P=0.003）和总生存期（HR=1.85，P=0.005 和 HR=1.67，P=0.02）更差，独立于国际预后指数。Hans 算法与 Wright 算法的相关性为 91%，kappa 检验几乎完全一致（0.81）。
我们的研究结果表明，在优化的标准化条件下，免疫组织化学定义的 COO 仍然是预测弥漫性大 B 细胞淋巴瘤预后的有用工具，BCL2 表达可能有助于识别有复发风险且可能对抗 BCL2 靶向药物有反应的老年患者。在这项前瞻性 III 期试验中，MYC 和 BCL2 的共表达似乎不能预测更差的生存。
NCT00144755。
