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Published on: January 9, 2019
Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) for PD-L1 testing in triple-negative breast cancer: a
Joe Yeong1,2,3, Tira Tan4, Zi Long Chow5,6
1Division of Pathology, Singapore General Hospital, Singapore joe.yeong.p.s@sgh.com.sg tan.puay.hoon@singhealth.com.sg.
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+ patient subgroup of the recent IMpassion130 trial. The SP142 PD-L1 antibody clone was used as a predictive assay in this trial, but this clone was found to be an outlier in previous harmonisation studies in lung cancer.
Aims:
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:
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:
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:
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.
Insights
Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) shows promise for evaluating programmed death-ligand 1 (PD-L1) clones in triple-negative breast cancer (TNBC). This method allows simultaneous quantification of multiple PD-L1 antibodies, aiding treatment response prediction.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Programmed death-ligand 1 (PD-L1) antibody therapy is approved for metastatic triple-negative breast cancer (TNBC), particularly in PD-L1 positive subgroups.
- The SP142 PD-L1 clone, used in the IMpassion130 trial, showed variability in previous lung cancer harmonization studies.
- Assessing PD-L1 clone comparability is crucial for accurate patient stratification in TNBC immunotherapy.
Purpose of the Study:
- To evaluate the concordance between conventional immunohistochemistry (IHC) and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) for PD-L1 assessment in TNBC.
- To compare three different PD-L1 antibody clones (22C3, SP142, SP263) simultaneously using mIHC/IF.
Main Methods:
- A cohort of 25 TNBC cases, 12 non-small-cell lung carcinomas, and 8 other cancers were analyzed.
- Conventional IHC and mIHC/IF techniques were employed to detect PD-L1 expression.
- Epithelial cell adhesion molecule (EpCAM) labeling distinguished tumor cells from immune cells.
Main Results:
- Moderate-to-strong correlations were observed between mIHC/IF and conventional IHC for PD-L1 positivity.
- Individual concordance rates across different PD-L1 clones ranged from 67% to 100%.
- Spearman's rank correlation coefficients reached up to 0.88, indicating good agreement.
Conclusions:
- mIHC/IF is a promising tool for simultaneously detecting and quantifying multiple PD-L1 clones in cancer immunotherapy.
- This method enables accurate evaluation of both tumor and immune cells, crucial for predicting patient response to anti-PD-1/PD-L1 therapy.
- Further harmonization and analysis are essential for integrating mIHC/IF into routine diagnostic settings for challenging cancers.
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