【病理资讯】免疫组化可以替代基因表达谱对非特异性外周T细胞淋巴瘤分类

2020-08-24

Reproducing the molecular subclassification of peripheral T-cell lymphoma–NOS by immunohistochemistry

Catalina Amador, Timothy C. Greiner, Tayla B. Heavican, Lynette M. Smith, Karen Tatiana Galvis, Waseem Lone, Alyssa Bouska, Francesco D’Amore, Martin Bjerregaard Pedersen, Stefano Pileri, Claudio Agostinelli, Andrew L. Feldman, Andreas Rosenwald, German Ott, Anja Mottok, Kerry J. Savage, Laurence de Leval, Philippe Gaulard, Soon Thye Lim, Choon Kiat Ong, Sarah L. Ondrejka, Joo Song, Elias Campo, Elaine S. Jaffe, Louis M. Staudt, Lisa M. Rimsza, Julie Vose, Dennis D. Weisenburger，Wing C. Chan, and Javeed Iqbal, on behalf of the lymphoma/Leukemia Molecular Profiling Project

Blood. 2019;134(24):2159-2170。

👇文献精选（含中文解读）

ABSTRACT：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.

原文献地址：

https://pubmed.ncbi.nlm.nih.gov/31562134/

免疫组化可以替代基因表达谱

对非特异性外周T细胞淋巴瘤分类

摘要：外周T细胞淋巴瘤(PTCL)是成熟T细胞的恶性肿瘤。其中约三分之一病例的最终病理诊断是非特异性PTCL(PTCL-NOS)。以前我们通过对肿瘤基因表达谱(GEP)的研究，发现PTCL-NOS 的两种主要分子亚型:PTCL-GATA3和PTCL-TBX21。这两种分子亚型在致癌途径和预后上存在显著差异。而在当前的研究中，我们尝试在肿瘤石蜡标本上，用免疫组化(IHC)的方法，根据对关键转录因子(GATA3和TBX21)及其靶标蛋白(CCR4和CXCR3)表达的研究进行类似的分类。此项研究在训练组和验证组两组病例中展开。训练组包括49个病例，每个病例都有完整的GEP数据。通过对训练组病例的研究发现免疫组化方法同样可以把PTCL-NOS 分成2个IHC亚型: PTCL-GATA3和PTCL-TBX21.与 GEP分类相比，匹配度达到85％。这两个免疫组化亚型在总体生存率上存在显著差异(P=0.03)。免疫组化分类方法简单易行，对训练组病例的研究证明在病理医生中有很高的观察者间可重复性。通过对PTCL-NOS验证组中的124个病例的研究我们也确认了PTCL-GATA3和PTCL-TBX21 IHC亚型之间在总体生存率上的显著统计学意义(P=0.003)。而通过多变量的分析，我们发现高国际预后指数得分(3-5)和PTCL-GATA3 IHC亚型是总体生存率的独立不良预测因子(P=0.0015)。此外这两个IHC亚型之间有明显不同的形态学特征(P<0.001)。而且PTCL-TBX21亚型主要是以CD8+细胞毒性T 细胞为主(P=0.03)。此项研究证明IHC的方法可以将PTCL-NOS分成两种亚型。临床上可以根据这样的分类对PTCL-NOS进行有效的预后风险评估并制定相应的治疗方案。

译者点评(Comments)

根据最新的WHO淋巴瘤分类(2017)，PTCL-NOS 可以根据基因表达谱分为GATA3 和TBX21两个分子亚型。两者致癌通路不同而且TBX21 亚型预后较好。然而在病理诊断实践中，分子分类的方法有很大的局限性。这篇发表在2019年底的文章证明血液病理医师可以利用TBX21, CXCR3, GATA3和CCR4四个抗体，依靠IHC 的方法快速准确地进行PTCL-NOS 的分类. TBX21 亚型：TBX21+ 或TBX21-/CXCR3+; GATA3亚型：TBX21-/CXCR3-/GATA3+或 TBX21-/CXCR3-/GATA3-/CCR4+. 尽管有极少数病例不符合这两种亚型的免疫组化特征，这种IHC 分类方法可以满足绝大多数情况的临床需求。译者认为本文的研究成果很有可能在将来得到广泛使用并成为PTCL-NOS分类的指南。