程序性死亡配体 1 在胃癌中的表达：与错配修复缺陷和 HER2 阴性状态的相关性。

Programmed death-ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2-negative status.

机构信息

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

出版信息

Cancer Med. 2018 Jun;7(6):2612-2620. doi: 10.1002/cam4.1502. Epub 2018 Apr 19.

DOI:10.1002/cam4.1502

PMID:29673110

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6010739/

Abstract

Gastric cancer (GC) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of PD-L1 and its prognostic value in GC. We aimed to evaluate the expression rates of PD-L1 in GC, and further assess its relationship with mismatch repair (MMR), and human epidermal growth factor receptor 2 (HER2) status. We retrospectively collected 550 consecutive cases of GC in Fudan University Shanghai Cancer Center from 2010 to 2012. PD-L1, MMR protein, and HER2 status were detected by immunohistochemistry (IHC). Fluorescence in situ hybridization was further used in HER2 IHC 2+ cases. Cases with at least 1% membranous and/or cytoplasmic PD-L1 staining in either tumor cells (TCs) or tumor-infiltrating immune cells (TIICs) were considered as PD-L1 positive. The correlation between clinicopathological parameters, HER2, MMR, and PD-L1 expression status was determined using chi-squared tests. About 37.3% cases (205/550) showed PD-L1 expression in TCs and/or TIICs. 17.3% cases (95/550) showed PD-L1 expression in TCs, 34.5% (190/550) cases showed PD-L1 expression in TIICs. There were 45 deficient MMR (dMMR) cases (8.2%), which showed higher rates of PD-L1 expression compared with MMR-proficient carcinomas (60.0% vs. 35.2%, P = 0.001). HER2 was positive in 66 (12.0%) cases. The expression of PD-L1 occurred more frequently in HER2-negative group than HER2-positive cohorts (39.0% vs. 24.2%, P = 0.020). The survival analysis revealed that PD-L1 was not associated with prognosis. This study evaluated the association between the PD-L1 expression and a specific subgroup (dMMR and HER2-negative) in a large Asian cohort of GC. GC patients with dMMR and HER2-negative status exhibited higher PD-L1 expression rates. Our finding indicated that MMR and HER-2 status might be potential biomarkers for anti-PD-L1 therapy.

摘要

胃癌（GC）是最常见的恶性肿瘤之一。免疫疗法是一种有前途的靶向治疗方法。免疫调节程序性死亡-1（PD-1）/程序性死亡配体 1（PD-L1）轴已被用作免疫治疗的检查点靶标。目前，关于 PD-L1 在 GC 中的表达状态及其预后价值存在很大差异。我们旨在评估 PD-L1 在 GC 中的表达率，并进一步评估其与错配修复（MMR）和人表皮生长因子受体 2（HER2）状态的关系。我们回顾性收集了 2010 年至 2012 年复旦大学附属肿瘤医院连续 550 例 GC 病例。通过免疫组织化学（IHC）检测 PD-L1、MMR 蛋白和 HER2 状态。HER2 IHC 2+病例进一步采用荧光原位杂交法。在肿瘤细胞（TCs）或肿瘤浸润免疫细胞（TIICs）中至少有 1%膜和/或细胞质 PD-L1 染色的病例被认为是 PD-L1 阳性。使用卡方检验确定临床病理参数、HER2、MMR 和 PD-L1 表达状态之间的相关性。约 37.3%的病例（205/550）在 TCs 和/或 TIICs 中显示 PD-L1 表达。17.3%的病例（95/550）在 TCs 中显示 PD-L1 表达，34.5%的病例（190/550）在 TIICs 中显示 PD-L1 表达。有 45 例错配修复缺陷（dMMR）病例（8.2%），与错配修复良好的癌相比，这些病例显示出更高的 PD-L1 表达率（60.0%比 35.2%，P=0.001）。HER2 阳性病例 66 例（12.0%）。PD-L1 的表达在 HER2 阴性组比 HER2 阳性组更频繁（39.0%比 24.2%，P=0.020）。生存分析显示 PD-L1 与预后无关。本研究在一个大型亚洲 GC 队列中评估了 PD-L1 表达与特定亚组（dMMR 和 HER2 阴性）之间的关系。dMMR 和 HER2 阴性的 GC 患者表现出更高的 PD-L1 表达率。我们的研究结果表明，MMR 和 HER-2 状态可能是抗 PD-L1 治疗的潜在生物标志物。