Yu Xiang-Yang, Zhang Xue-Wen, Wang Fang, Lin Yong-Bin, Wang Wei-Dong, Chen Yong-Qiang, Zhang Lan-Jun, Cai Ling
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
J Thorac Dis. 2018 Mar;10(3):1891-1902. doi: 10.21037/jtd.2018.03.14.
Aberrant expression of programmed cell death-ligand 1 (PD-L1) and protein 53 (P53) has been observed in various malignancies, and recently, the mechanism of PD-L1 regulation by P53 has been elucidated. We aimed to explore possible correlations between PD-L1 and P53 expression and the prognosis of patients with resected pulmonary lymphoepithelioma-like carcinoma (LELC).
A total of 67 consecutive patients with primary pulmonary LELC who underwent radical resection from January 2003 to December 2014 were enrolled in our study. Membranous PD-L1 and nuclear P53 expression were detected by immunohistochemical staining (IHC).
Positive expression of PD-L1 in tumor cells (TCs), PD-L1 in tumor-infiltrating lymphocytes (TILs) and P53 was investigated in 44 patients (65.7%), 37 patients (55.2%), and 34 patients (50.7%), respectively. Using univariate and multivariable analysis, both PD-L1 (+) in TCs and P53 (+) were observed to be significantly independent prognostic factors associated with longer disease-free survival (DFS, P=0.037 and 0.039, respectively), along with early stage LELC (P=0.037), but had no association with overall survival (OS) (P>0.05). In the P53 (+) group, the rate of patients with PD-L1 (+) in TCs was significantly higher than in the P53 (-) group (85.3% 45.5%, P=0.001). In addition, among the 45 patients who underwent adjuvant chemotherapy, DFS was significantly longer in patients with either PD-L1 (+) in TCs or P53 (+) (P=0.036 and 0.044, respectively).
PD-L1 and P53 may be potential therapeutic targets for primary pulmonary LELC. PD-L1 (+) in TCs and P53 (+) were reliable predictors for longer DFS and benefits from adjuvant therapy in resected cases. Routine detection of these two indices in lung LELC may be warranted.
程序性细胞死亡配体1(PD-L1)和蛋白53(P53)的异常表达已在多种恶性肿瘤中被观察到,并且最近,P53对PD-L1的调控机制已被阐明。我们旨在探讨PD-L1和P53表达之间可能的相关性以及肺淋巴上皮瘤样癌(LELC)切除患者的预后情况。
我们纳入了2003年1月至2014年12月期间连续67例行根治性切除的原发性肺LELC患者。通过免疫组织化学染色(IHC)检测膜性PD-L1和核P53的表达。
分别在44例患者(65.7%)、37例患者(55.2%)和34例患者(50.7%)中研究了肿瘤细胞(TCs)中PD-L1的阳性表达、肿瘤浸润淋巴细胞(TILs)中PD-L1的阳性表达以及P53的阳性表达。通过单因素和多因素分析,观察到TCs中PD-L1(+)和P53(+)均为与更长无病生存期(DFS,P分别为0.037和0.039)显著相关的独立预后因素,同时还有早期LELC(P = 0.037),但与总生存期(OS)无关(P>0.05)。在P53(+)组中,TCs中PD-L1(+)的患者比例显著高于P53(-)组(85.3%对45.5%,P = 0.001)。此外,在45例接受辅助化疗的患者中,TCs中PD-L1(+)或P53(+)的患者DFS显著更长(P分别为0.036和0.044)。
PD-L1和P53可能是原发性肺LELC的潜在治疗靶点。TCs中PD-L1(+)和P53(+)是切除病例中更长DFS以及辅助治疗获益的可靠预测指标。在肺LELC中常规检测这两个指标可能是有必要的。