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Anticancer Res. 2017 Dec;37(12):6771-6778.

Comparison of PD-L1 mRNA Expression Measured with the CheckPoint Typer® Assay with PD-L1 Protein Expression Assessed with Immunohistochemistry in Non-small Cell Lung Cancer.

Author information

1
Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany Ramona.erber@uk-erlangen.de.
2
Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
3
Department of Medicine 1 - Gastroenterology, Pneumonology and Endocrinology, University Hospital, Friedrich-Alexander University Erlangen- Nürnberg (FAU), Erlangen, Germany.
4
Department of Respiratory Medicine, Allergology and Sleep Medicine, Paracelsus Medical University Nuernberg, General Hospital Nuernberg, Nürnberg, Germany.
5
STRATIFYER Molecular Pathology GmbH, Köln, Germany.
6
Institute of Pathology, St. Elisabeth Hospital, Köln, Germany.

Abstract

BACKGROUND:

Immunohistochemical (IHC) assessment of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) has become important since the development of anti-PD-1/-PD-L1 directed drugs. Various PD-L1 antibodies and cut-offs have been used in different trials to predict response to these drugs, thus comparison of those studies is difficult. We compared PD-L1 mRNA expression measured by RT-qPCR with PD-L1 protein expression evaluated by IHC. Moreover, we investigated the impact of different tumour tissue acquisition methods on the reliability of PD-L1 measurement techniques.

MATERIALS AND METHODS:

NSCLC cases (N=22), including n=9 mediastinal lymph node biopsies acquired by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and n=5 metastases, were evaluated prospectively for PD-L1 protein on tumor cells (TC) and immune cells (IC) using E1L3N and 28-8 antibodies and PD-L1 mRNA using the CheckPoint TYPER® assay.

RESULTS:

In primary NSCLC tissues, agreement between PD-L1 mRNA and TC staining using the 28-8 antibody was excellent (ĸ=0.85, p=0.0002). Comparing both PD-L1 antibodies against each other showed a kappa value of 0.58 (p=0.0106). In EBUS-TBNA, PD-L1 mRNA correlated perfectly with the 28-8 antibody (ĸ=1.0, p=0.0023). PD-L1 mRNA levels significantly differed when comparing 28-8 TC staining of tumours >49% with 1-49% and 0% (p=0.0040; p=0.0081, respectively). In metastatic lesions, differences between PD-L1 mRNA and IHC became apparent (ĸ=0.2, p=0.2525).

CONCLUSION:

Testing of PD-L1 mRNA and 28-8 IHC showed an excellent agreement in NSCLC samples including mediastinal lymph node biopsies. Since PD-L1 expression in >50% TC detected by 28-8 IHC can be reliably detected by RT-qPCR, quantitative PD-L1 mRNA determination should be considered as an alternative to IHC as there is no interobserver variability in RNA results.

KEYWORDS:

28-8; E1L3N; EBUS-TBNA; NSCLC; PD-1; PD-L1; immunohistochemistry; lung cancer; mRNA; nivolumab; pembrolizumab

PMID:
29187455
DOI:
10.21873/anticanres.12137
[Indexed for MEDLINE]

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