Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China.
Department of Oncology, Shanghai Medical College, Shanghai, China.
Histopathology. 2019 Mar;74(4):618-628. doi: 10.1111/his.13765. Epub 2019 Jan 15.
The protein expression of programmed death-ligand 1 (PD-L1) has been recognised as being a biomarker for poor prognosis in diffuse large B-cell lymphoma (DLBCL). The aims of this study were to determine PD-L1 DNA status and mRNA status, and to explore whether they contribute to protein expression and their clinicopathological correlation in DLBCL.
In this study, we used fluorescence in-situ hybridisation, RNA in-situ hybridisation and immunohistochemistry to determine PD-L1 status at three different levels in 287 DLBCL samples with follow-up. Their correlation and clinical pathological relevance were also analysed. Our results showed that 1.7% (3/175) of patients had PD-L1 DNA amplification, 19.9% (57/287) had high PD-L1 mRNA expression, and 11.8% (34/287) had high PD-L1 protein expression. Both mRNA and protein expression of PD-L1 were significantly higher in non-germinal centre B-cell-like (GCB) DLBCL than in GCB DLBCL (P < 0.05). In addition, the patients with high PD-L1 mRNA or high PD-L1 protein expression but no PD-L1 DNA amplification had significantly poorer overall survival (OS) than those with low PD-L1 expression (P < 0.05). Furthermore, we found that PD-L1 mRNA and PD-L1 protein expression were highly correlated (P = 0.012), which was observed in all three samples with DNA amplification.
PD-L1 DNA amplification is a rare event, PD-L1 mRNA is the main contributor to the high PD-L1 protein expression, and the latter two will serve as important biomarkers for predicting the prognosis of DLBCL patients and selecting them for immunotherapy.
程序性死亡配体 1（PD-L1）的蛋白表达已被认为是弥漫性大 B 细胞淋巴瘤（DLBCL）预后不良的生物标志物。本研究旨在确定 PD-L1 的 DNA 状态和 mRNA 状态，并探讨它们是否有助于 DLBCL 中的蛋白表达及其与临床病理的相关性。
在这项研究中，我们使用荧光原位杂交、RNA 原位杂交和免疫组织化学方法在 287 例有随访的 DLBCL 样本中在三个不同水平上确定 PD-L1 状态，并分析其相关性和临床病理相关性。我们的结果显示，1.7%（3/175）的患者存在 PD-L1 DNA 扩增，19.9%（57/287）的患者存在高 PD-L1 mRNA 表达，11.8%（34/287）的患者存在高 PD-L1 蛋白表达。非生发中心 B 细胞样（GCB）DLBCL 中 PD-L1 mRNA 和蛋白表达均显著高于 GCB DLBCL（P<0.05）。此外，高 PD-L1 mRNA 或高 PD-L1 蛋白表达而无 PD-L1 DNA 扩增的患者总生存（OS）显著低于低 PD-L1 表达的患者（P<0.05）。此外，我们发现 PD-L1 mRNA 和 PD-L1 蛋白表达高度相关（P=0.012），在所有三个存在 DNA 扩增的样本中均观察到这种相关性。
PD-L1 DNA 扩增是一种罕见事件，PD-L1 mRNA 是导致 PD-L1 蛋白高表达的主要因素，后两者将作为预测 DLBCL 患者预后和选择其进行免疫治疗的重要生物标志物。
