Expression of FOXP3, CD68, and CD20 at Diagnosis in the Microenvironment of Classical Hodgkin Lymphoma Is Predictive of Outcome
Expression of FOXP3, CD68, and CD20 at Diagnosis in the Microenvironment of Classical Hodgkin Lymphoma Is Predictive of Outcome
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DOI：
10.1200/jco.2011.39.9881
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发表时间：
2013-01-10
影响因子：
45.3
通讯作者：
Gribben, John G.
中科院分区：
文献类型：
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作者：
Greaves, Paul;Clear, Andrew;Gribben, John G.
目的免疫微环境是经典霍奇金淋巴瘤（CHL）病理生理的关键。20%的患者最初治疗失败，其他人接受了过度毒性治疗。预后评分和生物标志物尚未显著影响预后。先前的生物标志物研究受到组织分析范围、统计不一致和未能验证结果的限制。我们的目标是克服这些局限性，在一个具有更大组织范围的新患者队列中验证最近发现的微环境生物标志物（CD68， FOXP3和CD20），并使用严格的统计方法。对122例CHL患者的诊断组织进行微阵列和染色，并使用自动化系统在每个患者10至20个高倍视野中计数阳性细胞。进行了两项统计分析：一项是分类分析，采用测试/验证集定义的切点和Kaplan-Meier估计的5年总生存（OS）、疾病特异性生存（DSS）和一线治疗失败（FFTF）的结果测量，另一项是独立的多变量分析，采用绝对未分类计数。结果CD20表达增加，OS改善。FOXP3表达升高可提高OS， CD68表达升高可降低FFTF和OS。FOXP3独立于CD68表达而变化，在多变量分析中作为连续变量分析时保持显著性。结合FOXP3和CD68的简单评分区分三组：FFTF 93%、62%和47% (P < 0.001)， DSS 93%、82%和63% (P = 0.03)， OS 93%、82%和59% （P = 0.002）。我们已经独立验证了CD68， FOXP3和CD20作为CHL的预后生物标志物，并且我们首次证明，据我们所知，FOXP3和CD68联合使用可能进一步改善预后分层。[J]中华医学杂志，31(3):526 - 526。(C)美国临床肿瘤学会2012
PurposeThe immune microenvironment is key to the pathophysiology of classical Hodgkin lymphoma (CHL). Twenty percent of patients experience failure of their initial treatment, and others receive excessively toxic treatment. Prognostic scores and biomarkers have yet to influence outcomes significantly. Previous biomarker studies have been limited by the extent of tissue analyzed, statistical inconsistencies, and failure to validate findings. We aimed to overcome these limitations by validating recently identified microenvironment biomarkers (CD68, FOXP3, and CD20) in a new patient cohort with a greater extent of tissue and by using rigorous statistical methodology.Patients and MethodsDiagnostic tissue from 122 patients with CHL was microarrayed and stained, and positive cells were counted across 10 to 20 high-powered fields per patient by using an automated system. Two statistical analyses were performed: a categorical analysis with test/validation set-defined cut points and Kaplan-Meier estimated outcome measures of 5-year overall survival (OS), disease-specific survival (DSS), and freedom from first-line treatment failure (FFTF) and an independent multivariate analysis of absolute uncategorized counts.ResultsIncreased CD20 expression confers superior OS. Increased FOXP3 expression confers superior OS, and increased CD68 confers inferior FFTF and OS. FOXP3 varies independently of CD68 expression and retains significance when analyzed as a continuous variable in multivariate analysis. A simple score combining FOXP3 and CD68 discriminates three groups: FFTF 93%, 62%, and 47% (P < .001), DSS 93%, 82%, and 63% (P = .03), and OS 93%, 82%, and 59% (P = .002).ConclusionWe have independently validated CD68, FOXP3, and CD20 as prognostic biomarkers in CHL, and we demonstrate, to the best of our knowledge for the first time, that combining FOXP3 and CD68 may further improve prognostic stratification. J Clin Oncol 31:256-262. (C) 2012 by American Society of Clinical Oncology