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.

Abstract

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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