Programmed death-ligand 1 expression associated with molecular characteristics in surgically resected lung adenocarcinoma

Zhengbo Song, Xinmin Yu, Guoping Cheng, Yiping Zhang

Several clinical trials have shown that immune treatment focus on programmed death-1 and programmed death-ligand 1 (PD-L1) yields a good clinical efficacy in advanced non-small cell lung cancer (NSCLC). We investigated whether the PD-L1 expression was related to clinicopathologic and molecular characteristics in patients with surgically resected NSCLC. Between December 2008 and 2013, formalin-fixed, paraffin-embedded samples were obtained from patients with lung adenocarcinoma at Zhejiang Cancer Hospital. RT-PCR was used to analyze EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2 mutations and ALK, ROS1, RET fusion genes. The PD-L1 expression was evaluated by immunohistochemistry and staining of 5 % or more was scored as positive expression. Survival analysis was evaluated using the Kaplan-Meier method. Multivariate regression was performed using the Cox proportional hazards model. Mutations were detected in 76.6 % of the 385 patients tested: EGFR mutation (n = 205, 53.2 %), followed by EML4-ALK rearrangement (n = 18, 4.7 %), KRAS (n = 16, 4.2 %), HER2 (n = 9, 2.3 %), ROS1 rearrangement (n = 8, 2.1 %), PIK3CA (n = 6, 1.6 %), RET rearrangement (n = 6,1.6 %), BRAF (n = 2, 0.5 %), and NRAS mutations (n = 1, 0.2 %). Twenty-four (6.2 %) patients carried coexisting mutations. PD-L1 expression was detected in 48.3 % (186/385) of all the patients. PD-L1 positive patients more frequently carried coexisting mutations (18/24, 75 %), followed by single-gene (145/271, 53.5 %) and pan-negative mutations (23/90, 25.6 %). PD-L1 expression decreased disease-free survival (DFS) in univariate analysis (P = 0.014). Multivariate analysis revealed that PD-L1 expression was not an independent risk factor for poor DFS and overall survival (OS) (P = 0.22 and 0.37, respectively). PD-L1 overexpression is more frequently observed in oncogene-mediated lung adenocarcinoma, especially with coexisting mutation subtypes. PD-L1 expression is not a prognostic factor in surgically resected lung adenocarcinoma patients.