Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
Lung Cancer. 2015 Jun;88(3):254-9. doi: 10.1016/j.lungcan.2015.03.017. Epub 2015 Mar 21.
Programmed cell death-ligand 1 (PD-L1) and driver mutations are found in non-small cell lung cancers (NSCLCs) and may be suitable targets for specific therapies, but their roles in lymphoepithelioma-like carcinoma (LELC) of the lung are unclear.
Sixty-six patients with pulmonary LELCs were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Tumors with moderate-to-strong membrane staining in ≥5% of tumor cells were positive for PD-L1 overexpression. The presence of driver mutations in the genes for epidermal growth factor receptor (EGFR), KRAS, and BRAF were examined by direct sequencing. Anaplastic lymphoma kinase (ALK) and ROS1 levels were determined by immunohistochemistry. Correlations of PD-L1 expression and driver mutations with clinicopathologic parameters were analyzed.
The overall frequency of PD-L1 overexpression and EGFR mutation was 75.8% and 12.1%, respectively. No KRAS, BRAF, ALK or ROS1 aberrations could be detected. PD-L1 expression was not associated with driver mutations. Multivariate analysis revealed that smoking and advanced stage were independent risk factors for poor overall survival, whereas PD-L1 positivity was not significantly associated with patient outcome.
There are high PD-L1 expression and infrequent driver mutations in LELCs compared with conventional NSCLCs. The high expression of PD-L1 in EBV and inflammation associated LELC may provide a rationale for immunotherapy in this subtype of lung cancer.
程序性死亡配体 1(PD-L1)和驱动基因突变存在于非小细胞肺癌(NSCLC)中,可能是特定治疗的合适靶点,但它们在肺淋巴上皮瘤样癌(LELC)中的作用尚不清楚。
对 66 例肺 LELC 患者进行了研究。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%的肿瘤细胞膜染色中度至强阳性为 PD-L1 过表达阳性。通过直接测序检测表皮生长因子受体(EGFR)、KRAS 和 BRAF 基因中的驱动突变。通过免疫组化检测间变性淋巴瘤激酶(ALK)和 ROS1 水平。分析 PD-L1 表达和驱动突变与临床病理参数的相关性。
PD-L1 过表达和 EGFR 突变的总体频率分别为 75.8%和 12.1%。未检测到 KRAS、BRAF、ALK 或 ROS1 异常。PD-L1 表达与驱动突变无关。多因素分析显示,吸烟和晚期是总生存不良的独立危险因素,而 PD-L1 阳性与患者预后无显著相关性。
与传统 NSCLC 相比,LELC 中存在高 PD-L1 表达和罕见的驱动基因突变。EBV 和炎症相关 LELC 中 PD-L1 的高表达可能为该亚型肺癌的免疫治疗提供依据。