Takada Kazuki, Toyokawa Gouji, Okamoto Tatsuro, Baba Shingo, Kozuma Yuka, Matsubara Taichi, Haratake Naoki, Akamine Takaki, Takamori Shinkichi, Katsura Masakazu, Shoji Fumihiro, Honda Hiroshi, Oda Yoshinao, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cancer Med. 2017 Nov;6(11):2552-2561. doi: 10.1002/cam4.1215. Epub 2017 Oct 4.
Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using F-fluorodeoxyglucose positron emission tomography/computed tomography ( F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD-L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD-L1 positivity. PD-L1-expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative F-FDG PET/CT was a predictor of PD-L1 protein expression in patients with NSCLC.
程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡配体1(PD-L1)已被确定为肺癌免疫治疗的新靶点。在本研究中,我们使用氟代脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(F-FDG PET/CT)评估肺癌的代谢特征,并分析其与PD-L1蛋白表达的关系。采用抗体克隆SP142通过免疫组织化学法评估579例手术切除的原发性肺癌患者的PD-L1蛋白表达。肿瘤细胞膜染色少于5%的病例被视为阴性。我们研究了术前F-FDG PET/CT中PD-L1蛋白表达频率与最大标准化摄取值(SUVmax)之间的关联。通过受试者工作特征曲线分析确定SUVmax的临界值。与无PD-L1蛋白表达的非小细胞肺癌(NSCLC)患者相比,有PD-L1蛋白表达的患者SUVmax显著更高(P < 0.0001)。然而,神经内分泌肿瘤患者的SUVmax与PD-L1蛋白表达之间无相关性(P = 0.6545)。多因素分析显示,吸烟、胸膜侵犯的存在和高SUVmax是PD-L1阳性的独立预测因素。表达PD-L1的NSCLC具有高糖代谢。术前F-FDG PET/CT中的SUVmax是NSCLC患者PD-L1蛋白表达的一个预测指标。