Clinical and pathologic features of lung cancer expressing programmed cell death ligand 1 (PD-L1)

被引:130
作者
Shimoji, Masaki [1 ]
Shimizu, Shigeki [2 ]
Sato, Katsuaki [1 ]
Suda, Kenichi [1 ]
Kobayashi, Yoshihisa [1 ]
Tomizawa, Kenji [1 ]
Takemoto, Toshiki [1 ]
Mitsudomi, Tetsuya [1 ]
机构
[1] Kindai Univ, Fac Med, Dept Surg, Div Thorac Surg, 377-2 Ohno Higashi, Osaka 5898511, Japan
[2] Hyogo Coll Med, Dept Mol Pathol, Nishinomiya, Hyogo 6638501, Japan
关键词
Lung cancer; PD-L1; EMT; Prognostic factor; Adenocarcinoma; EPITHELIAL-MESENCHYMAL TRANSITION; POOR-PROGNOSIS; ADENOCARCINOMA; MUTATIONS; DOCETAXEL; CARCINOMA; NIVOLUMAB; ANTIBODY; SAFETY; B7-H1;
D O I
10.1016/j.lungcan.2016.04.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:69 / 75
页数:7
相关论文
共 24 条
[1]   Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall- cell lung cancer [J].
Azuma, K. ;
Ota, K. ;
Kawahara, A. ;
Hattori, S. ;
Iwama, E. ;
Harada, T. ;
Matsumoto, K. ;
Takayama, K. ;
Takamori, S. ;
Kage, M. ;
Hoshino, T. ;
Nakanishi, Y. ;
Okamoto, I. .
ANNALS OF ONCOLOGY, 2014, 25 (10) :1935-1940
[2]   Tumor B7-H1 and B7-H3 Expression in Squamous Cell Carcinoma of the Lung [J].
Boland, Jennifer M. ;
Kwon, Eugene D. ;
Harrington, Susan M. ;
Wampfler, Jason A. ;
Tang, Hui ;
Yang, Ping ;
Aubry, Marie Christine .
CLINICAL LUNG CANCER, 2013, 14 (02) :157-163
[3]   Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].
Borghaei, H. ;
Paz-Ares, L. ;
Horn, L. ;
Spigel, D. R. ;
Steins, M. ;
Ready, N. E. ;
Chow, L. Q. ;
Vokes, E. E. ;
Felip, E. ;
Holgado, E. ;
Barlesi, F. ;
Kohlhaeufl, M. ;
Arrieta, O. ;
Burgio, M. A. ;
Fayette, J. ;
Lena, H. ;
Poddubskaya, E. ;
Gerber, D. E. ;
Gettinger, S. N. ;
Rudin, C. M. ;
Rizvi, N. ;
Crino, L. ;
Blumenschein, G. R. ;
Antonia, S. J. ;
Dorange, C. ;
Harbison, C. T. ;
Finckenstein, F. Graf ;
Brahmer, J. R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639
[4]   Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].
Brahmer, Julie ;
Reckamp, Karen L. ;
Baas, Paul ;
Crino, Lucio ;
Eberhardt, Wilfried E. E. ;
Poddubskaya, Elena ;
Antonia, Scott ;
Pluzanski, Adam ;
Vokes, Everett E. ;
Holgado, Esther ;
Waterhouse, David ;
Ready, Neal ;
Gainor, Justin ;
Aren Frontera, Osvaldo ;
Havel, Libor ;
Steins, Martin ;
Garassino, Marina C. ;
Aerts, Joachim G. ;
Domine, Manuel ;
Paz-Ares, Luis ;
Reck, Martin ;
Baudelet, Christine ;
Harbison, Christopher T. ;
Lestini, Brian ;
Spigel, David R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135
[5]   Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].
Brahmer, Julie R. ;
Tykodi, Scott S. ;
Chow, Laura Q. M. ;
Hwu, Wen-Jen ;
Topalian, Suzanne L. ;
Hwu, Patrick ;
Drake, Charles G. ;
Camacho, Luis H. ;
Kauh, John ;
Odunsi, Kunle ;
Pitot, Henry C. ;
Hamid, Omid ;
Bhatia, Shailender ;
Martins, Renato ;
Eaton, Keith ;
Chen, Shuming ;
Salay, Theresa M. ;
Alaparthy, Suresh ;
Grosso, Joseph F. ;
Korman, Alan J. ;
Parker, Susan M. ;
Agrawal, Shruti ;
Goldberg, Stacie M. ;
Pardoll, Drew M. ;
Gupta, Ashok ;
Wigginton, Jon M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465
[6]   Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression [J].
Chen, Limo ;
Gibbons, Don L. ;
Goswami, Sangeeta ;
Cortez, Maria Angelica ;
Ahn, Young-Ho ;
Byers, Lauren A. ;
Zhang, Xuejun ;
Yi, Xiaohui ;
Dwyer, David ;
Lin, Wei ;
Diao, Lixia ;
Wang, Jing ;
Roybal, Jonathon D. ;
Patel, Mayuri ;
Ungewiss, Christin ;
Peng, David ;
Antonia, Scott ;
Mediavilla-Varela, Melanie ;
Robertson, Gordon ;
Jones, Steve ;
Suraokar, Milind ;
Welsh, James W. ;
Erez, Baruch ;
Wistuba, Ignacio I. ;
Chen, Lieping ;
Peng, Di ;
Wang, Shanshan ;
Ullrich, Stephen E. ;
Heymach, John V. ;
Kurie, Jonathan M. ;
Qin, F. Xiao-Feng .
NATURE COMMUNICATIONS, 2014, 5
[7]  
Chen YB, 2012, TUMORI, V98, P751, DOI 10.1700/1217.13499
[8]   Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer In what state is this art? [J].
Kerr, Keith M. ;
Tsao, Ming-Sound ;
Nicholson, Andrew G. ;
Yatabe, Yasushi ;
Wistuba, Ignacio I. ;
Hirsch, Fred R. .
JOURNAL OF THORACIC ONCOLOGY, 2015, 10 (07) :985-989
[9]   Clinicopathological analysis of PD-L1 and PD-L2 expression in pulmonary squamous cell carcinoma: Comparison with tumor-infiltrating T cells and the status of oncogenic drivers [J].
Kim, Moon-Young ;
Koh, Jaemoon ;
Kim, Sehui ;
Go, Heounjeong ;
Jeon, Yoon Kyung ;
Chung, Doo Hyun .
LUNG CANCER, 2015, 88 (01) :24-33
[10]   Molecular mechanisms of epithelial-mesenchymal transition [J].
Lamouille, Samy ;
Xu, Jian ;
Derynck, Rik .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (03) :178-196