Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
Blood. 2012 Sep 13;120(11):2290-6. doi: 10.1182/blood-2012-05-430389. Epub 2012 Jun 26.
Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.
通过基因表达谱分析,已经发现了能够预测弥漫性大 B 细胞淋巴瘤患者生存的生物学因素,如细胞起源和基质特征。我们试图模拟这些基因表达谱分析的结果,并基于免疫组织化学创建一个新的生物学预后模型。我们研究了 199 例(训练组 125 例,验证组 74 例)初治弥漫性大 B 细胞淋巴瘤患者,这些患者接受了利妥昔单抗联合 CHOP(环磷酰胺、多柔比星、长春新碱和泼尼松)或 CHOP 样治疗,并对石蜡包埋组织微阵列进行了免疫组织化学染色。在该模型中,每种不良预后因素得 1 分:非生发中心 B 细胞样亚型、SPARC(富含半胱氨酸的酸性分泌蛋白)<5%和微血管密度四分位第 4 位。在调整国际预后指数后,该模型在训练组和验证组的多变量分析中均高度预测了总生存和无事件生存。该新模型通过 3 个生物学标志物来描绘 2 组患者,一组具有低生物学评分(0-1)和良好的生存,另一组具有高评分(2-3)和较差的生存。这种新的生物学预后模型可以与国际预后指数结合,用于新型或风险适应治疗的患者分层。