【病理資訊】免疫組化可以替代基因表達譜對非特異性外周T細胞淋巴瘤分類
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。
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.
原文獻地址：
https://pubmed.ncbi.nlm.nih.gov/31562134/
免疫組化可以替代基因表達譜
對非特異性外周T細胞淋巴瘤分類
摘要：外周T細胞淋巴瘤(PTCL)是成熟T細胞的惡性腫瘤。其中約三分之一病例的最終病理診斷是非特異性PTCL(PTCL-NOS)。以前我們通過對腫瘤基因表達譜(GEP)的研究，發現PTCL-NOS 的兩種主要分子亞型:PTCL-GATA3和PTCL-TBX21。這兩種分子亞型在致癌途徑和預后上存在顯著差異。而在當前的研究中，我們嘗試在腫瘤石蠟標本上，用免疫組化(IHC)的方法，根據對關鍵轉錄因子(GATA3和TBX21)及其靶標蛋白(CCR4和CXCR3)表達的研究進行類似的分類。此項研究在訓練組和驗證組兩組病例中展開。訓練組包括49個病例，每個病例都有完整的GEP數據。通過對訓練組病例的研究發現免疫組化方法同樣可以把PTCL-NOS 分成2個IHC亞型: PTCL-GATA3和PTCL-TBX21.與 GEP分類相比，匹配度達到85％。這兩個免疫組化亞型在總體生存率上存在顯著差異(P=0.03)。免疫組化分類方法簡單易行，對訓練組病例的研究證明在病理醫生中有很高的觀察者間可重復性。通過對PTCL-NOS驗證組中的124個病例的研究我們也確認了PTCL-GATA3和PTCL-TBX21 IHC亞型之間在總體生存率上的顯著統計學意義(P=0.003)。而通過多變量的分析，我們發現高國際預后指數得分(3-5)和PTCL-GATA3 IHC亞型是總體生存率的獨立不良預測因子(P=0.0015)。此外這兩個IHC亞型之間有明顯不同的形態學特征(P<0.001)。而且PTCL-TBX21亞型主要是以CD8+細胞毒性T 細胞為主(P=0.03)。此項研究證明IHC的方法可以將PTCL-NOS分成兩種亞型。臨床上可以根據這樣的分類對PTCL-NOS進行有效的預后風險評估并制定相應的治療方案。
譯者點評(Comments)
根據最新的WHO淋巴瘤分類(2017)，PTCL-NOS 可以根據基因表達譜分為GATA3 和TBX21兩個分子亞型。兩者致癌通路不同而且TBX21 亞型預后較好。然而在病理診斷實踐中， 分子分類的方法有很大的局限性。這篇發表在2019年底的文章證明血液病理醫師可以利用TBX21, CXCR3, GATA3和CCR4四個抗體，依靠IHC 的方法快速準確地進行PTCL-NOS 的分類. TBX21 亞型：TBX21+ 或TBX21-/CXCR3+; GATA3亞型：TBX21-/CXCR3-/GATA3+或 TBX21-/CXCR3-/GATA3-/CCR4+. 盡管有極少數病例不符合這兩種亞型的免疫組化特征，這種IHC 分類方法可以滿足絕大多數情況的臨床需求。譯者認為本文的研究成果很有可能在將來得到廣泛使用并成為PTCL-NOS分類的指南。
相關文獻
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