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Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma

Authors Zhang Y, Wang L, Li Y, Pan Y, Wang R, Hu H, Li H, Luo X, Ye T, Sun Y, Chen H

Received 1 January 2014

Accepted for publication 11 February 2014

Published 12 April 2014 Volume 2014:7 Pages 567—573

DOI https://doi.org/10.2147/OTT.S59959

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Yang Zhang,1,2,* Lei Wang,1,2,* Yuan Li,2,3 Yunjian Pan,1,2 Rui Wang,1,2 Haichuan Hu,1,2 Hang Li,1,2 Xiaoyang Luo,1,2 Ting Ye,1,2 Yihua Sun,1,2 Haiquan Chen1,2

1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China

*These authors contributed equally to this work

Background: The clinicopathologic characteristics of tumors expressing programmed death (PD-1) ligands (PD-Ls) PD-L1 or PD-L2 and their associations with common driver mutations in lung adenocarcinoma are not clearly defined, despite the progression of anti-PD-1/PD-L1 immunotherapy.
Methods: PD-L1 and PD-L2 expression was measured by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinical variables, histologic subtypes, and the mutational status of EGFR, KRAS, HER2, and ALK.
Results: Positive PD-L1 expression was significantly associated with more advanced T status, N status, and pathologic stage. Histologically, lung adenocarcinomas with positive PD-L1 staining were less likely to be adenocarcinoma in situ or minimally invasive adenocarcinoma and more likely to have solid predominant subtype. Both PD-L1 expression (odds ratio =1.984, 95% confidence interval =1.010–3.894; P=0.047) and PD-L2 expression (odds ratio =2.328, 95% confidence interval =1.201–4.512; P=0.012) were independent predictors of poor overall survival. When the combined PD-L expression and pathologic stage were used together to predict overall survival, the concordance index increased to 0.763, and the Akaike information criteria value decreased to 356.08.
Conclusion: We defined the clinicopathologic features of lung adenocarcinomas with high expression of PD-L1 and PD-L2. We further demonstrated the role of PD-L expression as a useful prognostic marker for lung adenocarcinoma.

Keywords: immunotherapy, lung cancer, prognostic markers, oncogenic driver mutations

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