Copyright
©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma
Ryul Kim, Bhumsuk Keam, Dohee Kwon, Chan-Young Ock, Miso Kim, Tae Min Kim, Hak Jae Kim, Yoon Kyung Jeon, In Kyu Park, Chang Hyun Kang, Dong-Wan Kim, Young Tae Kim, Dae Seog Heo
Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea
Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea
Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
Dohee Kwon, Department of Pathology, Seoul National University Hospital, Seoul 03080, South Korea
Hak Jae Kim, Department of Radiation Oncology, Seoul National University Hospital, Seoul 03080, South Korea
Yoon Kyung Jeon, Department of Pathology, Seoul National University Hospital, Seoul 03080, South Korea
Yoon Kyung Jeon, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
In Kyu Park, Chang Hyun Kang, Young Tae Kim, Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul 03080, South Korea
Author contributions: Kim R and Keam B designed the concept of the study; Keam B, Kim M, Kim TM, Kim DW and Heo DS provided study patients and chemotherapy; Park IK, Kang CH and Kim YT provided study patients and surgery; Kim HJ provided study patients and radiation therapy; Kim R gathed data, statistical analysis and interpretation; Kwon D and Jeon YK contributed to the pathologic analysis of tissue microarray; Kim R wrote this manuscript.
Supported by Seoul National University Hospital Research Fund, No. 03-2015-0380; Ministry of Health and Welfare, South Korea, No. HI06C0874.
Institutional review board statement: This study was approved by the Seoul National University Hospital Institutional Review Board (IRB approval number: H-1405-055-579) and was conducted in accordance with Declaration of Helsinki provisions.
Informed consent statement: Patient informed consent was waived due to the retrospective design of the study.
Conflict-of-interest statement: The authors have no conflicts of interest to declare or other disclosures of record.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at bhumsuk@snu.ac.kr. Gaining informed consent for publication of the dataset from participants is not possible because of the retrospective design of this study. However, publication of this data does not compromise anonymity or confidentiality or breach local data protection laws, for the dataset to be considered for publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Bhumsuk Keam, MD, PhD, Clinical Associate Professor, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea. bhumsuk@snu.ac.kr
Telephone: +82-2-20727215 Fax: +82-2-7642199
Received: June 1, 2016
Peer-review started: June 2, 2016
First decision: July 12, 2016
Revised: July 27, 2016
Accepted: August 23, 2016
Article in press: August 23, 2016
Published online: October 7, 2016
AIM
To investigate the expression and prognostic role of programmed death ligand-1 (PD-L1) in locally advanced esophageal squamous cell carcinoma (ESCC).
METHODS
A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed.
RESULTS
Tumor tissues from 67 ESCC patients (33.5%) were PD-L1-positive. Positive p16 expression was observed in 21 specimens (10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens (21.0%). Although PD-L1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PD-L1-positivity (OR = 2.34, 95%CI: 1.16-4.72, P = 0.017). PD-L1 expression was not significantly associated with a change in overall survival (P = 0.656). In contrast, the locoregional relapse rate tended to increase (P = 0.134), and the distant metastasis rate was significantly increased (HR = 1.72, 95%CI: 1.01-2.79, P = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative ESCC.
CONCLUSION
PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC.
Core tip: The clinical significance of expression of programmed death ligand-1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) has not yet been fully established. We analyzed tissue microarrays of surgical specimen of 200 ESCC patients by immunohistochemistry with antibodies directed against PD-L1, p16, and c-Met. Our results suggest that tumors from approximately one-third of the ESCC patients are positive for PD-L1 expression, and PD-L1 expression is positively correlated with c-Met expression. Although PD-L1 positivity was not found to be associated with survival of ESCC patients, we show that it may play a critical role in distant failure and progression of ESCC.
