Liang Xiaolong, Sun Jian, Wu Huanwen, Luo Yufeng, Wang Lili, Lu Junliang, Zhang Zhiwen, Guo Junchao, Liang Zhiyong, Liu Tonghua
Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuai Fu Yuan, Wangfujing, Beijing, 100730, People's Republic of China.
Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuai Fu Yuan, Wangfujing, Beijing, 100730, People's Republic of China.
Diagn Pathol. 2018 Jan 17;13(1):5. doi: 10.1186/s13000-017-0678-4.
Programmed death ligand 1 (PD-L1) has shown potential as a therapeutic target in numerous solid tumors. Its prognostic significance has also been established in pancreatic ductal adenocarcinoma (PDAC). The present study aimed to explore PD-L1 expression in PDAC cases in a large Chinese cohort using an in vitro diagnostic (IVD) assay to provide further insight into the potential value of programmed cell death protein 1 (PD-1) as a therapeutic target.
Three hundred seventy-three PDAC patients were retrospectively recruited in this study. Tissue microarray (TMA) blocks were made from available formalin-fixed and paraffin-embedded (FFPE) tumor and matched adjacent tissue specimens. We evaluated PD-L1 protein expression via immunohistochemistry (IHC) using a U.S. Food and Drug Administration (FDA)-approved IVD assay. The relationships between PD-L1 positivity and both clinicopathological characteristics and patient prognosis were analyzed. PD-1 expression and clinicopathological significance were also evaluated.
PD-L1 and PD-1 positivity were observed in 3.2% and 7.5% of cases, respectively. PD-L1 showed a predominantly membranous pattern in tumor cells, while no positive PD-L1 staining was observed in normal regions. Statistical analyses revealed that PD-L1 expression was associated with lymph node metastasis. PD-L1 positivity was a prognostic indicator of progression-free survival (PFS) and overall survival (OS) in univariate analyses, but only PFS remained statistically significant in multivariate analysis. PD-1 expression was detected in lymphocytes and was not associated with any clinicopathological feature except a history of pancreatitis.
The PD-L1 positivity rate is low in PDAC when evaluated using a companion diagnostic assay. It remains an independent prognostic factor for poor PFS.
程序性死亡配体1（PD-L1）已显示出在多种实体瘤中作为治疗靶点的潜力。其在胰腺导管腺癌（PDAC）中的预后意义也已得到证实。本研究旨在使用体外诊断（IVD）检测方法，在中国的一个大型队列中探索PDAC病例中的PD-L1表达情况，以进一步深入了解程序性细胞死亡蛋白1（PD-1）作为治疗靶点的潜在价值。
本研究回顾性招募了373例PDAC患者。组织微阵列（TMA）块由可用的福尔马林固定石蜡包埋（FFPE）肿瘤及匹配的相邻组织标本制成。我们使用美国食品药品监督管理局（FDA）批准的IVD检测方法，通过免疫组织化学（IHC）评估PD-L1蛋白表达。分析了PD-L1阳性与临床病理特征及患者预后之间的关系。还评估了PD-1表达及临床病理意义。
分别在3.2%和7.5%的病例中观察到PD-L1和PD-1阳性。PD-L1在肿瘤细胞中主要呈膜性模式，而在正常区域未观察到阳性PD-L1染色。统计分析显示，PD-L1表达与淋巴结转移相关。在单因素分析中，PD-L1阳性是无进展生存期（PFS）和总生存期（OS）的预后指标，但在多因素分析中只有PFS仍具有统计学意义。在淋巴细胞中检测到PD-1表达，除胰腺炎病史外，其与任何临床病理特征均无关联。
使用伴随诊断检测方法评估时，PDAC中PD-L1阳性率较低。它仍然是PFS不良的独立预后因素。
