title: Programmed death-ligand 1 expression associated with molecular characteristics in surgically resected lung adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, People's Republic of China.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, 310022, Zhejiang, People's Republic of China.
authors.forename: Zhengbo
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, People's Republic of China.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, 310022, Zhejiang, People's Republic of China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, People's Republic of China. zjzlyy16@163.com.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, 310022, Zhejiang, People's Republic of China. zjzlyy16@163.com.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D060890:B7-H1 Antigen
keywords: Coexisting mutations; Gene mutation; Lung adenocarcinoma; Non-small cell lung cancer; Prognosis; Programmed cell deathligand 1