Zhao Liang, Liao Xiyi, Hong Ganji, Zhuang Yanzhen, Fu Kaili, Chen Peiqiong, Wang Yuhuan, Chen Haojun, Lin Qin
Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China,
Department of Pathology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China.
Cancer Manag Res. 2019 Feb 19;11:1631-1640. doi: 10.2147/CMAR.S193878. eCollection 2019.
To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment.
A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining.
Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I-III accounted for 35 (49.3%) cases, while stage IVa-IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage (=0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein-Barr virus DNA load (=0.021), N stage (=0.009), M stage (=0.014), and clinical stage (=0.001).
dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted.
分析鼻咽癌(NPC)中的错配修复(MMR)状态和程序性死亡受体配体1(PD-L1)表达,并研究PD-L1和MMR状态是否可作为预测免疫检查点阻断(ICB)治疗反应的生物标志物。
2017年12月至2018年9月期间,共有108例患者经组织病理学确诊为NPC。所有组织标本均在任何治疗前采集。通过免疫组织化学和聚合酶链反应(PCR)确定肿瘤组织的MMR状态。采用免疫组织化学方法分析NPC组织中PD-L1的表达。肿瘤细胞(TC)或肿瘤浸润免疫细胞(TIIC)中PD-L1高表达定义为相应细胞中≥50%出现膜染色。
在获得书面知情同意后,从102例患者中获取了组织样本。71例(69.6%)患者确诊后在我院接受治疗。Ⅰ-Ⅲ期疾病占35例(49.3%),而Ⅳa-Ⅳb期有36例(50.7%)。102例患者中仅2例通过免疫组织化学和PCR被鉴定为错配修复缺陷(dMMR)。在102例NPC病例中的77例(75.5%)中证实TC中存在PD-L1高表达,而102例NPC病例中仅13例(12.7%)被认为TIIC中存在PD-LI高表达。TC中的PD-L1表达与T分期呈正相关(=0.033),而TIIC中的PD-L1表达与血浆EB病毒DNA载量呈负相关(=0.021)、与N分期呈负相关(=0.009)、与M分期呈负相关(=0.014)以及与临床分期呈负相关(=0.001)。
dMMR在NPC中是罕见事件,在临床实践中可能不是预测ICB治疗有效性的前瞻性生物标志物。还确定NPC中PD-L1高表达相当常见,并强调了区分TC和TIIC中PD-L1表达的重要性。