Masaki Shimoji1, Shigeki Shimizu2, Katsuaki Sato1, Kenichi Suda1, Yoshihisa Kobayashi1, Kenji Tomizawa1, Toshiki Takemoto1, Tetsuya Mitsudomi3. 1. Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama 589-8511, Japan. 2. Department of Molecular Pathology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan. 3. Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama 589-8511, Japan. Electronic address: mitsudom@surg.med.kindai.ac.jp.
Abstract
BACKGROUND: Programmed cell death 1 (PD-1) negatively regulates antigen receptor signaling upon binding by either of its ligands, programmed cell death ligand 1 or 2 (PD-L1/2). Blockade of this interaction with either PD-1 or PD-L1 antibodies has been successful in the treatment of human cancer, especially melanoma and non-small cell lung cancer. PD-L1 expression has been proposed as a predictor of tumor response. However, the relationships between PD-L1 expression and various clinicopathological characteristics remain unclear. MATERIALS AND METHODS: PD-L1 expression was examined in 220 non-small cell lung cancer specimens that were consecutively resected at our hospital after validating the E1L3N antibody immunohistochemical assay by comparing IHC and RT-PCR data for lung cancer cell lines. We evaluated the relationships between PD-L1 positivity, several clinical factors and the immunohistochemical expression of epithelial-mesenchymal transition (EMT), cancer stem cell and proliferative markers. RESULTS: PD-L1 was expressed in 22% of lung adenocarcinomas and 60% of squamous cell lung cancers. There was no significant association between PD-L1 expression and clinicopathological features in squamous cell lung cancer. However, in patients with lung adenocarcinoma, PD-L1 expression was significantly correlated with solid subtype histology, vimentin expression, increased Ki-67 labeling index and poor prognosis by multivariate analysis. CONCLUSION: PD-L1 expression was associated with high proliferative activity and the EMT phenotype in adenocarcinoma but not in squamous cell carcinoma of the lung. PD-L1 expression was a significant poor prognostic factor in patients with lung adenocarcinoma.
BACKGROUND: Programmed cell death 1 (PD-1) negatively regulates antigen receptor signaling upon binding by either of its ligands, programmed cell death ligand 1 or 2 (PD-L1/2). Blockade of this interaction with either PD-1 or PD-L1 antibodies has been successful in the treatment of humancancer, especially melanoma and non-small cell lung cancer. PD-L1 expression has been proposed as a predictor of tumor response. However, the relationships between PD-L1 expression and various clinicopathological characteristics remain unclear. MATERIALS AND METHODS:PD-L1 expression was examined in 220 non-small cell lung cancer specimens that were consecutively resected at our hospital after validating the E1L3N antibody immunohistochemical assay by comparing IHC and RT-PCR data for lung cancer cell lines. We evaluated the relationships between PD-L1 positivity, several clinical factors and the immunohistochemical expression of epithelial-mesenchymal transition (EMT), cancer stem cell and proliferative markers. RESULTS:PD-L1 was expressed in 22% of lung adenocarcinomas and 60% of squamous cell lung cancers. There was no significant association between PD-L1 expression and clinicopathological features in squamous cell lung cancer. However, in patients with lung adenocarcinoma, PD-L1 expression was significantly correlated with solid subtype histology, vimentin expression, increased Ki-67 labeling index and poor prognosis by multivariate analysis. CONCLUSION:PD-L1 expression was associated with high proliferative activity and the EMT phenotype in adenocarcinoma but not in squamous cell carcinoma of the lung. PD-L1 expression was a significant poor prognostic factor in patients with lung adenocarcinoma.
Authors: Kenichi Suda; Leslie Rozeboom; Christopher J Rivard; Hui Yu; Kim Ellison; Mary Ann C Melnick; Trista K Hinz; Daniel Chan; Lynn E Heasley; Katerina Politi; Tetsuya Mitsudomi; Fred R Hirsch Journal: Lung Cancer Date: 2017-04-19 Impact factor: 5.705
Authors: Rathi N Pillai; Madhusmita Behera; Taofeek K Owonikoko; Alice O Kamphorst; Suchita Pakkala; Chandra P Belani; Fadlo R Khuri; Rafi Ahmed; Suresh S Ramalingam Journal: Cancer Date: 2017-09-28 Impact factor: 6.860
Authors: Matthew Evans; Brendan O'Sullivan; Frances Hughes; Tina Mullis; Matthew Smith; Nicola Trim; Philippe Taniere Journal: Pathol Oncol Res Date: 2018-09-17 Impact factor: 3.201