TY - JOUR
T1 - Interobserver agreement of pd‐l1/sp142 immunohistochemistry and tumor‐infiltrating lymphocytes (Tils) in distant metastases of triple‐negative breast cancer
T2 - A proof‐of‐concept study. a report on behalf of the international immuno‐oncology biomarker working group
AU - van Bockstal, Mieke R.
AU - Cooks, Maxine
AU - Nederlof, Iris
AU - Brinkhuis, Mariël
AU - Dutman, Annemiek
AU - Koopmans, Monique
AU - Kooreman, Loes
AU - van der Vegt, Bert
AU - Verhoog, Leon
AU - Vreuls, Celine
AU - Westenend, Pieter
AU - Kok, Marleen
AU - van Diest, Paul J.
AU - Nauwelaers, Inne
AU - Laudus, Nele
AU - Denkert, Carsten
AU - Rimm, David
AU - Siziopikou, Kalliopi P.
AU - Ely, Scott
AU - Zardavas, Dimitrios
AU - Roberts, Mustimbo
AU - Floris, Giuseppe
AU - Hartman, Johan
AU - Acs, Balazs
AU - Peeters, Dieter
AU - Bartlett, John M. S.
AU - Dequeker, Els
AU - Salgado, Roberto
AU - Giudici, Fabiola
AU - Michiels, Stefan
AU - Horlings, Hugo
AU - van Deurzen, Carolien H. M.
N1 - Funding Information: Conflicts of Interest: J.M.S.B. received research funding from Thermo Fisher Scientific, Genoptix, Agendia, Nanostring Technologies Inc., Stratifyer GmbH and Biotheranostics Inc., as well as hono‐ raria from NanoString Technologies Inc., Oncology Education, Biotheranostics Inc., and Med‐ comXchange Communications Inc. M.K. received institutional funding from AZ, BMS, and Roche. MK is an advisory board member of BMS, Daiichi, MSD, and Roche. C. van Deurzen received fund‐ ing for this study from Roche. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The other authors declare no conflict of interest. Funding Information: Funding: This research was funded by Roche (recipient: C.H.M. van Deurzen). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - Atezolizumab
KW - Distant metastasis
KW - Immune cells
KW - Interobserver variability
KW - PD‐L1
KW - SP142
KW - TILs
KW - TNBC
KW - Triple‐negative breast cancer
KW - Tumor‐infiltrating lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=85115966282&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers13194910
DO - https://doi.org/10.3390/cancers13194910
M3 - Article
C2 - 34638394
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 19
M1 - 4910
ER -