High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy
High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy
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DOI：
10.3324/haematol.2010.037408
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Campo, Elias
中科院分区：
文献类型：
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作者：
Cardesa-Salzmann, Teresa M.;Colomo, Luis;Campo, Elias
背景弥漫性大B细胞淋巴瘤是一种临床和分子异质性疾病。基因表达谱研究表明，肿瘤微环境影响生存和血管生成相关的签名是有害的。组织病理学微血管密度对免疫化疗治疗的弥漫性大B细胞淋巴瘤的生存率的影响尚不清楚。本研究的目的是评估两个独立系列的弥漫性大B细胞淋巴瘤患者的组织病理学微血管密度与immunotherapy.Design和MethodsOne一百四十七例白血病淋巴瘤分子特征项目（培训系列）和118例患者从加泰罗尼亚淋巴瘤研究组GELCAB（验证队列）的预后影响包括在研究中。用CD 31对微血管进行免疫染色，并用计算机图像分析系统进行定量。110例白血病淋巴瘤分子特征项目病例中定义的间质评分被用来分析与微血管密度data.ResultsMicrovessel密度的相关性与间质评分显着相关（r = 0.3209; P < 0.001）。在训练系列（4年OS 54% vs. 78%; P = 0.004）和验证队列（57% vs. 81%; P = 0.006）中，微血管密度高的患者的总生存率显著低于微血管密度低的患者。在多变量分析中，两组中高微血管密度均为独立于国际预后指数的具有统计学意义的不利预后因素[训练系列：国际预后指数（相对风险2.7; P = 0.003）;微血管密度（相对风险1.96; P = 0.002）;验证队列：国际预后指数（相对危险度4.74; P < 0.001）;微血管密度（相对风险2.4; P = 0.016）]。结论这些发现强调了血管生成对弥漫性大B-淋巴瘤患者预后的影响。细胞淋巴瘤和在临床试验中评价抗血管生成药物的兴趣。
BackgroundDiffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy.Design and MethodsOne hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data.ResultsMicrovessel density significantly correlated with the stromal score (r = 0.3209; P < 0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P = 0.004) and in the validation cohort (57% vs. 81%; P = 0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P = 0.003); microvessel density (relative risk 1.96; P = 0.002); validation cohort: international prognostic index (relative risk 4.74; P < 0.001); microvessel density (relative risk 2.4; P = 0.016)].ConclusionsThese findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.