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Mod Pathol. 2015 Sep;28(9):1154-66. doi: 10.1038/modpathol.2015.63. Epub 2015 Jul 17.

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status.

Author information

1
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
2
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
4
Department of Genetic Epidemiology and Preventive Medicine, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
5
Department of Thoracic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
6
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
7
Ischemic/Hypoxia Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

Abstract

Immunotherapies targeting the programmed cell death-1/programmed cell death-ligand 1 pathway have emerged as promising therapeutic strategies for lung cancer. However, the expression pattern and prognostic implications of programmed cell death-ligand 1 and 2 and programmed cell death-1 in comparison with the histology and genetic alterations in pulmonary adenocarcinomas remains unclear and thus were addressed here. Programmed cell death-ligand 1 and 2 expression in tumor cells and the quantities of programmed cell death-1(+) and CD8(+) tumor-infiltrating lymphocytes were immunohistochemically evaluated in 497 resected pulmonary adenocarcinomas and analyzed according to clinicopathological and genetic statuses. Programmed cell death-ligand 1 and 2 expression were observed in 59% and 64% of pulmonary adenocarcinomas, respectively, and showed a strong positive correlation with each other (P < 0.001). Programmed cell death-ligand 1 expression was higher in nodal metastasis cases (P = 0.006), smokers (P = 0.056), poorly differentiated tumors and histologic subtypes of solid and micropapillary patterns (P < 0.001). There was no significant difference in programmed cell death-ligand 1 and 2 expression according to EGFR mutation status. However, programmed cell death-ligand 1 expression was correlated with ALK translocation (P =0.054) and expression of EGFR and MET (P < 0.001). Meanwhile, programmed cell death-ligand 2 expression was correlated with ALK translocation (P = 0.052), and expression of MET (P < 0.001) and ERBB2 (P = 0.013). The numbers of CD8(+) and programmed cell death-1(+) lymphocytes were higher in smokers (P = 0.012 and 0.016) and MET-expressing adenocarcinomas (P < 0.001). Patients expressing programmed cell death-ligand 1 and/or high ratios of programmed cell death-1(+)/CD8(+) lymphocytes showed shorter disease-free survival (P = 0.001). Our study demonstrated that programmed cell death-ligand 1 and 2 expression varied with histology, EGFR, ALK, MET, and ERBB2 statuses, and activation of the programmed cell death-1/programmed cell death-ligand 1 pathway may be a poor prognostic factor in pulmonary adenocarcinomas.

PMID:
26183759
DOI:
10.1038/modpathol.2015.63
[Indexed for MEDLINE]
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