Poor concordance among nine immunohistochemistry classifiers of cell-of-origin for diffuse large B-cell lymphoma: implications for therapeutic strategies.
Poor concordance among nine immunohistochemistry classifiers of cell-of-origin for diffuse large B-cell lymphoma: implications for therapeutic strategies.
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DOI：
10.1158/1078-0432.ccr-13-1482
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发表时间：
2013-12-15
期刊：
影响因子：
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通讯作者：
Gribben JG
中科院分区：
文献类型：
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作者：
Coutinho R;Clear AJ;Owen A;Wilson A;Matthews J;Lee A;Alvarez R;Gomes da Silva M;Cabeçadas J;Calaminici M;Gribben JG
在弥漫性大B细胞淋巴瘤（DLBCL）中，基于肿瘤细胞的分子特征改善治疗选择的机会即将到来。药物如硼替佐米对不良结果活化的B细胞型DLBCL表现出选择性活性。为了使靶向治疗在这种疾病中取得成功，需要将患者分成具有高可靠性的分子组的强有力的策略。虽然分子研究被认为是金标准，但已经发表了几种免疫组织化学（IHC）算法，声称能够根据细胞来源对患者进行分层，并与患者结局相关。然而，独立组的结果重现性较差。我们在DLBCL诊断活检数据集中研究了9种用于分子分类的IHC算法，包括CD 10、BCL 6、BCL 2、MUM 1、FOXP 1、GCET 1和LMO 2的免疫染色。三名专家观察员对IHC图谱进行了评估并达成一致。基于所有评分组合和每个组合的受试者数量的共识矩阵允许评估可靠性。使用Kaplan-Meier曲线和对数秩检验评价个体标志物和分类器的生存影响。不同算法之间患者分类的一致性较低。只有4%的肿瘤被归类为GCB和21%的ABC/非GCB的所有方法。在R-CHOP治疗队列中，这些算法均未提供预后信息。需要进一步的工作来标准化用于DLBCL细胞来源分类的IHC算法，以使这些算法被认为是用于临床决策的基于分子的方法的可靠替代方案。
The opportunity to improve therapeutic choices on the basis of molecular features of the tumour cells is on the horizon in Diffuse Large B-cell Lymphoma (DLBCL). Agents such as bortezomib exhibit selective activity against the poor outcome activated B-cell type DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. While molecular studies are considered gold standard, several immunohistochemistry (IHC) algorithms have been published that claim to be able to stratify patients according to their cell-of-origin and to be relevant for patient outcome. However results are poorly reproducible by independent groups. We investigated nine IHC algorithms for molecular classification in a dataset of DLBCL diagnostic biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1 and LMO2. IHC profiles were assessed and agreed among three expert observers. A consensus matrix based on all scoring combinations and the number of subjects for each combination allowed to assess reliability. The survival impact of individual markers and classifiers was evaluated using Kaplan-Meier curves and the log-rank test. The concordance in patient’s classification across the different algorithms was low. Only 4% the tumors have been classified as GCB and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP treated cohort. Further work is required to standardize IHC algorithms for DLBCL cell-of-origin classification for these to be considered reliable alternatives to molecular-based methods to be used for clinical decisions.