摘要

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell malignancies; approximately one-third of cases are designated as PTCL-not otherwise specified (PTCL-NOS). Using gene-expression profiling (GEP), we have previously defined 2 major molecular subtypes of PTCL-NOS, PTCL-GATA3 and PTCL-TBX21, which have distinct biological differences in oncogenic pathways and prognosis. In the current study, we generated an immunohistochemistry (IHC) algorithm to identify the 2 subtypes in paraffin tissue using antibodies to key transcriptional factors (GATA3 and TBX21) and their target proteins (CCR4 and CXCR3). In a training cohort of 49 cases of PTCL-NOS with corresponding GEP data, the 2 subtypes identified by the IHC algorithm matched the GEP results with high sensitivity (85%) and showed a significant difference in overall survival (OS) (P = .03). The IHC algorithm classification showed high interobserver reproducibility among pathologists and was validated in a second PTCL-NOS cohort (n = 124), where a significant difference in OS between the PTCL-GATA3 and PTCL-TBX21 subtypes was confirmed (P = .003). In multivariate analysis, a high International Prognostic Index score (3-5) and the PTCL-GATA3 subtype identified by IHC were independent adverse predictors of OS (P = .0015). Additionally, the 2 IHC-defined subtypes were significantly associated with distinct morphological features (P < .001), and there was a significant enrichment of an activated CD8+ cytotoxic phenotype in the PTCL-TBX21 subtype (P = .03). The IHC algorithm will aid in identifying the 2 subtypes in clinical practice, which will aid the future clinical management of patients and facilitate risk stratification in clinical trials.

译文

外周 T 细胞淋巴瘤 (PTCL) 是一组成熟 T 细胞恶性肿瘤; 大约 3分之1 的病例被指定为 PTCL-没有另外指定 (PTCL-NOS)。利用基因表达谱 (GEP),我们先前定义了 PTCL-NOS 的 2 个主要分子亚型,PTCL-GATA3 和 PTCL-TBX21,它们在致癌途径和预后方面具有明显的生物学差异。在目前的研究中,我们生成了一种免疫组织化学 (IHC) 算法,使用关键转录因子 (GATA3 和 TBX21) 的抗体来识别石蜡组织中的 2 种亚型以及它们的靶蛋白 (CCR4 和 CXCR3)。在 49 例具有相应 GEP 数据的 PTCL-NOS 患者的训练队列中,IHC 算法确定的 2 种亚型与 GEP 结果匹配,灵敏度高 (85%) 并显示出显著的总生存期 (OS) 差异 (P =。 03)。IHC 算法分类在病理学家中显示出高观察者之间的可重复性,并在第二个 PTCL-NOS 队列 (n = 124) 中得到验证, 其中 PTCL-GATA3 亚型和 PTCL-TBX21 亚型之间的 OS 有显著差异 (P =。 003)。在多变量分析中,高国际预后指数评分 (3-5) 和 IHC 确定的 PTCL-GATA3 亚型是 OS 的独立不良预测因素 (P =.0015)。此外,2 个 IHC 定义的亚型与不同的形态特征显著相关 (P <。 001),并且在 PTCL-TBX21 亚型中存在明显富集的活化 CD8 细胞毒性表型 (P = 0。 03)。IHC 算法将有助于在临床实践中识别这两种亚型,这将有助于未来患者的临床管理,并促进临床试验中的风险分层。

Immunohistochemistry

肾内泌尿 基础研究 实验技术
概述  :  

免疫组织化学又简称为免疫组化,是应用免疫学基本原理——抗原抗体反应,即抗原与抗体特异性结合的原理,通过化学反应使标记抗体的显色剂(荧光素、酶、金属离子或是同位素)显色,利用光学显微镜、荧光显微镜或电子显微镜进行实验结果观察,从而确定组织细胞内抗原(多肽或者蛋白质),对其进行定位、定性以及定量的研究,称之为免疫组织化学技术,又可称为免疫细胞化学(ICC,immunocytochemistry)。该技术是病理诊断中常规的技术手段。   原理

Immunohistochemistry   /'ɪmjʊnəʊ,hɪstəʊ'kemɪstrɪ/ 

释    义   免疫组织化学

同根词   immunological   adj. 免疫学的

例    句   The RPE cells were identified by DOPA staining and immunohistochemistry. 用多巴(DOPA)染色和免疫组织化学鉴定RPE细胞。

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