Slack Graham W, Steidl Christian, Sehn Laurie H, Gascoyne Randy D
Centre for Lymphoid Cancers, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada.
Br J Haematol. 2014 Dec;167(5):608-17. doi: 10.1111/bjh.13085. Epub 2014 Aug 19.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable therapeutic responses and alternative therapies are needed for patients with unfavourable treatment outcomes after standard treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). One promising candidate is brentuximab vedotin, an antibody-drug conjugate targeting CD30-expressing cells. However, CD30 (TNFRSF8) expression patterns in DLBCL are not well described thus far. Here, we examined CD30 expression in a population-based cohort of immunocompetent patients from British Columbia with de novo DLBCL using immunohistochemistry. 385 cases of formalin-fixed paraffin-embedded DLBCL in tissue microarrays were evaluated. 95 cases (25%) harboured CD30+ tumour cells. Using a > 0% cut-off, CD30 expression was predictive of superior 5-year progression-free survival within R-CHOP treated germinal centre B-cell-like (GCB) DLBCL (86% vs. 64%, P = 0·020), which was independent of the International Prognostic Index. Epstein-Barr virus (EBV) was identified in 11 (3%) cases, all of which were non-GCB (P = 0·001) and almost exclusively positive for CD30 expression (10/11) (P < 0·001). We conclude CD30 is expressed in a substantial proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic marker in R-CHOP treated GCB-DLBCL. The significant association of CD30 with EBV-positive non-GCB DLBCL suggests a distinct pathobiology for these cases.
弥漫性大B细胞淋巴瘤（DLBCL）是一种异质性疾病，治疗反应各异，对于接受R-CHOP（利妥昔单抗、环磷酰胺、阿霉素、长春新碱、泼尼松）标准治疗后治疗效果不佳的患者，需要替代疗法。一种有前景的候选药物是本妥昔单抗，一种靶向表达CD30细胞的抗体药物偶联物。然而，迄今为止，DLBCL中CD30（肿瘤坏死因子受体超家族8）的表达模式尚未得到充分描述。在此，我们使用免疫组织化学方法，对来自不列颠哥伦比亚省的一组具有免疫活性的初发性DLBCL患者队列中的CD30表达进行了检测。对组织芯片中385例福尔马林固定石蜡包埋的DLBCL病例进行了评估。95例（25%）含有CD30+肿瘤细胞。采用>0%的临界值，CD30表达可预测接受R-CHOP治疗的生发中心B细胞样（GCB）DLBCL患者5年无进展生存率更高（86%对64%，P = 0.020），这与国际预后指数无关。在11例（3%）病例中检测到爱泼斯坦-巴尔病毒（EBV），所有这些病例均为非GCB（P = 0.001），且几乎全部CD30表达呈阳性（10/11）（P < 0.001）。我们得出结论，CD30在相当一部分DLBCL中表达，CD30免疫组织化学可能是R-CHOP治疗的GCB-DLBCL中一个有用的预后标志物。CD30与EBV阳性非GCB DLBCL的显著关联提示这些病例具有独特的病理生物学特征。
