Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Mieke R. Van Bockstal, Maxine Cooks, Iris Nederlof, Mariel Brinkhuis, Annemiek Dutman, Monique Koopmans, Loes Kooreman, Bert van der Vegt, Leon Verhoog, Celine Vreuls, Pieter Westenend, Marleen Kok, Paul J. van Diest, Inne Nauwelaers, Nele Laudus, Carsten Denkert, David Rimm, Kalliopi P. Siziopikou, Scott Ely, Dimitrios ZardavasMustimbo Roberts, Giuseppe Floris, Johan Hartman, Balazs Acs, Dieter Peeters, John M. S. Bartlett, Els Dequeker, Roberto Salgado, Fabiola Giudici, Stefan Michiels, Hugo Horlings, Carolien H.M. van Deurzen

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Abstract

Patients with advanced triple‐negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD‐L1/SP142‐positive immune cells. Numbers of tumor‐infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter‐pathologist agreement in the assessment of PD‐L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD‐L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD‐L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD‐ L1 status (positive versus negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD‐L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD‐L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD‐L1 status of primary TNBCs.

Original languageEnglish
Article number4910
JournalCancers
Volume13
Issue number19
DOIs
Publication statusPublished - Oct 2021

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