Research Papers:

Concordance of programmed death-ligand 1 expression between primary and metastatic non-small cell lung cancer by immunohistochemistry and RNA in situ hybridization

Hye Ryun Kim, Yoon Jin Cha, Min Hee Hong, Manoj Gandhi, Shauna Levinson, Inkyung Jung, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho _, Sang-Jun Ha and Hyo Sup Shim

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Oncotarget. 2017; 8:87234-87243. https://doi.org/10.18632/oncotarget.20254

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Hye Ryun Kim1, Yoon Jin Cha2, Min Hee Hong1, Manoj Gandhi3, Shauna Levinson3, Inkyung Jung4, Jin Gu Lee5, Chang Young Lee5, Byoung Chul Cho1,6,*, Sang-Jun Ha7,* and Hyo Sup Shim2,*

1Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea

2Department of Pathology, Yonsei University College of Medicine, Seoul, Korea

3Thermo Fisher Scientific 3450 Central Expressway, Santa Clara, CA, USA

4Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul, Korea

5Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea

6JE-UK Institute for Cancer Research, JEUK Co., Ltd., Gumi, Korea

7Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea

*These authors have contributed equally to this study

Correspondence to:

Byoung Chul Cho, email: [email protected]

Sang-Jun Ha, email: [email protected]

Hyo Sup Shim, email: [email protected]

Keywords: programmed death ligand-1, non-small cell lung cancer, immunohistochemistry, RNA in situ hybridization

Received: April 21, 2017     Accepted: July 12, 2017     Published: August 14, 2017


We investigated the concordance of programmed death-ligand 1 (PD-L1) expression between primary cancer at initial diagnosis and metastasis at recurrence in resected non-small cell lung cancer (NSCLC). PD-L1 expression was evaluated using the SP142 assay in 37 NSCLC patients with paired primary lung cancer and surgically resected metastases at recurrence. PD-L1 positivity was defined as immunohistochemistry (IHC) and also evaluated by RNA in situ hybridization (RISH). The concordance rate of PD-L1 between primaries and metastases and correlation with clinicopathological factors were analyzed. PD-L1 expression was higher in squamous cell carcinoma, wild-type EGFR, and smokers than in non-squamous carcinoma, mutant EGFR, and never smokers, respectively. PD-L1 positivity was observed in 18.9% of primaries and 21.6% of metastases. IHC demonstrated 78.4% concordance of PD-L1 positivity between primary and metastatic cancers. In 10.8% of cases, PD-L1 positivity was higher in primaries than in metastases, and vice versa in the remaining 10.8%. By PD-L1 RISH, 35.1% of primaries and 27.0% of metastases demonstrated PD-L1 positivity. There was 62.2% concordance in PD-L1 by RISH between the primaries and metastases. Our results thus highlight the clinical importance of replacing metastases with primary archival tissue, particularly when re-biopsy is difficult at recurrence.

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