Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei 10002, Taiwan.
Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, No. 25, Ln. 442, Sec. 1, Jingguo Road, East Dist, Hsinchu City 30059, Taiwan.
Eur J Cancer. 2014 May;50(7):1361-9. doi: 10.1016/j.ejca.2014.01.018. Epub 2014 Feb 15.
Programmed cell death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable targets for specific immunotherapy. This study investigated the expression of PD-L1 in surgically resected stage I adenocarcinomas and correlated this with known major driver mutations and clinical outcomes.
One hundred and sixty-three patients with surgically resected stage I adenocarcinomas were explored. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in ⩾ 5% of tumour cells were scored as positive for PD-L1 overexpression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing and anaplastic lymphoma kinase (ALK) by immunohistochemistry. The correlations of PD-L1 expression with major driver mutations and clinicopathologic parameters were analysed.
The overall frequency of PD-L1 overexpression was 39.9% (65/163). PD-L1 had higher positive results in tumours with higher grade differentiation and vascular invasion and PD-L1 expression was not associated with the expressions of EGFR, KRAS, BRAF and ALK. Multivariate analysis revealed that abnormal carcinoembryonic antigen (CEA) and higher grade of differentiation were risk factors for poor relapse-free survival (RFS) and PD-L1 expression correlated with better RFS. Advanced pathologic stage was the independent risk for poor overall survival (OS).
The PD-L1 expression can be used as a prognostic indicator predictive of RFS in patients with surgically resected stage I lung adenocarcinomas. There may be a possibility for immunotherapy targeting the PD-L1 pathway in patients with lung adenocarcinoma in the future.
程序性死亡配体 1（PD-L1）在一组癌症中表达，这些癌症可能是特定免疫疗法的合适靶点。本研究调查了手术切除的 I 期腺癌中 PD-L1 的表达，并将其与已知的主要驱动突变和临床结果相关联。
研究了 163 例手术切除的 I 期腺癌患者。使用 PD-L1 抗体对石蜡包埋的肿瘤切片进行染色。肿瘤细胞中 ⩾5%的肿瘤细胞有中等至强的膜染色的肿瘤被评为 PD-L1 过表达阳性。通过直接测序检查驱动突变表皮生长因子受体（EGFR）、克氏大鼠肉瘤病毒癌基因同源物（KRAS）和 v-raf 鼠肉瘤病毒癌基因同源物 B（BRAF），通过免疫组织化学检查间变性淋巴瘤激酶（ALK）。分析了 PD-L1 表达与主要驱动突变和临床病理参数的相关性。
PD-L1 过表达的总体频率为 39.9%（65/163）。在分化程度较高和血管侵犯的肿瘤中，PD-L1 的阳性结果更高，PD-L1 的表达与 EGFR、KRAS、BRAF 和 ALK 的表达无关。多变量分析显示，异常癌胚抗原（CEA）和较高的分化程度是无复发生存（RFS）不良的危险因素，而 PD-L1 表达与较好的 RFS 相关。晚期病理分期是总生存（OS）不良的独立危险因素。
PD-L1 的表达可以作为手术切除的 I 期肺腺癌患者 RFS 的预后指标。未来，针对肺腺癌患者的 PD-L1 通路进行免疫治疗可能是一种可能。
