Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) for PD-L1 testing in triple-negative breast cancer: a translational assay compared with conventional IHC.


Journal

Journal of clinical pathology
ISSN: 1472-4146
Titre abrégé: J Clin Pathol
Pays: England
ID NLM: 0376601

Informations de publication

Date de publication:
Sep 2020
Historique:
received: 06 10 2019
revised: 23 12 2019
accepted: 31 12 2019
pubmed: 24 1 2020
medline: 1 9 2020
entrez: 24 1 2020
Statut: ppublish

Résumé

Programmed death-ligand 1 (PD-L1) monoclonal antibody therapy has recently gained approval for treating metastatic triple-negative breast cancer (TNBC) -, in particular in the PD-L1 To address the comparability of PD-L1 clones in TNBC, we evaluated the concordance between conventional immunohistochemistry (IHC) and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) that allowed simultaneous quantification of three different PD-L1 antibodies (22C3, SP142 and SP263). Our cohort comprised 25 TNBC cases, 12 non-small-cell lung carcinomas and 8 other cancers. EpCAM labelling was used to distinguish tumour cells from immune cells. Moderate-to-strong correlations in PD-L1 positivity were found between results obtained through mIHC/IF and IHC. Individual concordance rates in the study ranged from 67% to 100%, with Spearman's rank correlation coefficient values up to 0.88. mIHC/IF represents a promising tool in the era of cancer immunotherapy, as it can simultaneously detect and quantify PD-L1 labelling with multiple antibody clones, and allow accurate evaluation of tumour and immune cells. Clinicians and pathologists require this information to predict patient response to anti-PD-1/PD-L1 therapy. The adoption of this assay may represent a significant advance in the management of therapeutically challenging cancers. Further analysis and assay harmonisation are essential for translation to a routine diagnostic setting.

Sections du résumé

BACKGROUND BACKGROUND
Programmed death-ligand 1 (PD-L1) monoclonal antibody therapy has recently gained approval for treating metastatic triple-negative breast cancer (TNBC) -, in particular in the PD-L1
AIMS OBJECTIVE
To address the comparability of PD-L1 clones in TNBC, we evaluated the concordance between conventional immunohistochemistry (IHC) and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) that allowed simultaneous quantification of three different PD-L1 antibodies (22C3, SP142 and SP263).
METHODS METHODS
Our cohort comprised 25 TNBC cases, 12 non-small-cell lung carcinomas and 8 other cancers. EpCAM labelling was used to distinguish tumour cells from immune cells.
RESULTS RESULTS
Moderate-to-strong correlations in PD-L1 positivity were found between results obtained through mIHC/IF and IHC. Individual concordance rates in the study ranged from 67% to 100%, with Spearman's rank correlation coefficient values up to 0.88.
CONCLUSIONS CONCLUSIONS
mIHC/IF represents a promising tool in the era of cancer immunotherapy, as it can simultaneously detect and quantify PD-L1 labelling with multiple antibody clones, and allow accurate evaluation of tumour and immune cells. Clinicians and pathologists require this information to predict patient response to anti-PD-1/PD-L1 therapy. The adoption of this assay may represent a significant advance in the management of therapeutically challenging cancers. Further analysis and assay harmonisation are essential for translation to a routine diagnostic setting.

Identifiants

pubmed: 31969377
pii: jclinpath-2019-206252
doi: 10.1136/jclinpath-2019-206252
doi:

Substances chimiques

Antibodies, Monoclonal 0
B7-H1 Antigen 0
Biomarkers, Tumor 0
CD274 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

557-562

Informations de copyright

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: ZLC is a medical student from the University of Tasmania on a research elective posting with the Department of Anatomical Pathology Singapore General Hospital, supported by the Royal College of Pathologists of Australasia (RCPA) medical students’ scholarship. BL is part of the SIgN Immunomonitoring platform (supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011).

Auteurs

Joe Yeong (J)

Division of Pathology, Singapore General Hospital, Singapore joe.yeong.p.s@sgh.com.sg tan.puay.hoon@singhealth.com.sg.
Integrative Biology for Theranostics, Institute of Molecular Cell Biology, Agency of Science, Technology and Research (A*STAR), Singapore.
Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore.

Tira Tan (T)

Division of Medical Oncology, National Cancer Centre Singapore, Singapore.

Zi Long Chow (ZL)

Division of Pathology, Singapore General Hospital, Singapore.
University of Tasmania, Hobart, Tasmania, Australia.

Qing Cheng (Q)

Duke-NUS Medical School, Duke-NUS Medical School, Singapore.

Bernett Lee (B)

Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore.

Amanda Seet (A)

Division of Medical Oncology, National Cancer Centre Singapore, Singapore.

Johnathan Xiande Lim (JX)

Division of Pathology, Singapore General Hospital, Singapore.

Jeffrey Chun Tatt Lim (JCT)

Integrative Biology for Theranostics, Institute of Molecular Cell Biology, Agency of Science, Technology and Research (A*STAR), Singapore.

Clara Chong Hui Ong (CCH)

Division of Pathology, Singapore General Hospital, Singapore.
Department of Anatomical Pathology, Singapore General Hospital, Singapore.

Aye Aye Thike (AA)

Division of Pathology, Singapore General Hospital, Singapore.

Sahil Saraf (S)

Division of Pathology, Singapore General Hospital, Singapore.

Benjamin Yong Cheng Tan (BYC)

Division of Pathology, Singapore General Hospital, Singapore.

Yong Cheng Poh (YC)

Diagnostics Development (DxD) Hub, Agency of Science, Technology and Research (A*STAR), Singapore.

Sidney Yee (S)

Diagnostics Development (DxD) Hub, Agency of Science, Technology and Research (A*STAR), Singapore.

Jin Liu (J)

Duke-NUS Medical School, Duke-NUS Medical School, Singapore.

Elaine Lim (E)

Division of Medical Oncology, National Cancer Centre Singapore, Singapore.

Jabed Iqbal (J)

Division of Pathology, Singapore General Hospital, Singapore.

Rebecca Dent (R)

Division of Medical Oncology, National Cancer Centre Singapore, Singapore.

Puay Hoon Tan (PH)

Division of Pathology, Singapore General Hospital, Singapore joe.yeong.p.s@sgh.com.sg tan.puay.hoon@singhealth.com.sg.

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Classifications MeSH