Kim Seung Tae, Ha Sang Yun, Lee Sujin, Ahn Soomin, Lee Jeeyun, Park Se Hoon, Park Joon Oh, Lim Ho Yeong, Kang Won Ki, Kim Kyoung-Mee, Park Young Suk
1. Division of Hematology-Oncology, Department of Medicine.
2. Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Cancer. 2016 Feb 5;7(5):484-9. doi: 10.7150/jca.13711. eCollection 2016.
Programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells, interacts with PD1 expressed on the surface of T cells, inhibiting the T cells and blocking the antitumor immune response. Expression of PD-L1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. We investigated the impact of PD-L1 expression in 32 patients with metastatic GEP-NET. The expression of PD-L1 was evaluated using an anti-PD-L1 immunohistochemistry (IHC) antibody optimized for staining of formalin-fixed paraffin-embedded (FFPE) tissue samples. The correlation between PD-L1 and clinicopathological data including survival and response to systemic treatments was analyzed. Primary sites were 24 foregut-derived GEP-NETs, including stomach (n=1), duodenum (n=2), biliary tract (n=7), and pancreas (n=14), and 8 hindgut-derived GEP-NETs of the distal colon and rectum. Among the 32 patients with metastatic GEP-NET analyzed in this study, 7 (21.9%) had expression of PD-L1 in tumor tissues. Expression of PD-L1 was significantly associated with high-grade WHO classification (grade 3) (p=0.008) but not with gender, primary site, and number of metastatic sites (p>0.05). The status of PD-L1 expression was statistically associated with progression-free survival (PFS) for first-line systemic treatment (p=0.047). Moreover, the status of PD-L1 expression could significantly predict overall survival (p=0.037). The expression of PD-L1 was associated with higher WHO tumor grade (grade 3) in metastatic GEP-NETs. PD-L1 expression had both predictive and prognostic value for survival of patients with metastatic GEP-NETs.
程序性死亡配体1(PD-L1)在许多癌细胞上表达,它与T细胞表面表达的PD1相互作用,抑制T细胞并阻断抗肿瘤免疫反应。尚未对胃肠胰神经内分泌肿瘤(GEP-NETs)中PD-L1的表达进行研究。我们调查了32例转移性GEP-NET患者中PD-L1表达的影响。使用针对福尔马林固定石蜡包埋(FFPE)组织样本染色优化的抗PD-L1免疫组织化学(IHC)抗体评估PD-L1的表达。分析了PD-L1与临床病理数据(包括生存和对全身治疗的反应)之间的相关性。原发部位包括24例源自前肠的GEP-NET,其中胃(n = 1)、十二指肠(n = 2)、胆道(n = 7)和胰腺(n = 14),以及8例源自后肠的远端结肠和直肠GEP-NET。在本研究分析的32例转移性GEP-NET患者中,7例(21.9%)肿瘤组织中有PD-L1表达。PD-L1的表达与世界卫生组织高级别分类(3级)显著相关(p = 0.008),但与性别、原发部位和转移部位数量无关(p>0.05)。PD-L1表达状态与一线全身治疗的无进展生存期(PFS)在统计学上相关(p = 0.047)。此外,PD-L1表达状态可显著预测总生存期(p = 0.037)。在转移性GEP-NET中,PD-L1的表达与世界卫生组织肿瘤高级别(3级)相关。PD-L1表达对转移性GEP-NET患者的生存具有预测和预后价值。