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

Cancers

Dimitrios Zardavas¹  Fabiola Giudici²  Stefan Michiels²  Giuseppe Floris³  Carolien H. M. van Deurzen⁴  Balazs Acs⁵  Johan Hartman⁵  Mieke R. Van Bockstal⁶  Maxine Cooks⁷  Roberto Salgado⁸  Loes Kooreman⁹  Bert van der Vegt^1,10  Paul J. van Diest^1,11  Celine Vreuls^1,11  David Rimm^1,12  Inne Nauwelaers^1,13  Els Dequeker^1,13  Nele Laudus^1,13  Hugo Horlings^1,14  Marleen Kok^1,15  Iris Nederlof^1,15  Dieter Peeters^1,16  Carsten Denkert^1,17  Annemiek Dutman^1,18  Mariël Brinkhuis^1,19  John M.S. Bartlett^2,20  Monique Koopmans^2,21  Pieter Westenend^2,22  Leon Verhoog^2,23  Kalliopi P. Siziopikou^2,24  Scott Ely^2,25  Mustimbo Roberts^2,25 

[1] BMS Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ 08540, USA;Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, 94805 Villejuif, France;Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research, KU Leuven–University of Leuven, 3000 Leuven, Belgium;Department of Medicine, Yale School of Medicine, New Haven, CT 06510, USA;Department of Oncology and Pathology, CCK, Karolinkska Institutet, 17177 Stockholm, Sweden;Department of Pathology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium;Department of Pathology, Erasmus Medical Center Cancer Institute, 3015 GD Rotterdam, The Netherlands;Department of Pathology, GZA-ZNA Hospitals, 2050 Antwerp, Belgium;Department of Pathology, Maastricht University Medical Center (MUMC), 6229 HX Maastricht, The Netherlands;Department of Pathology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands;Department of Pathology, University Medical Center Utrecht (UMCU), 3584 CX Utrecht, The Netherlands;Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA;Department of Public Health and Primary Care, Biomedical Quality Assurance Research Unit, University of Leuven, Kapucijnenvoer 35d, 3000 Leuven, Belgium;Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;Division of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;HistoGenex NV, 2610 Antwerp, Belgium;Institute of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Baldingerstr. 1, 35043 Marburg, Germany;Isala, 8025 AB Zwolle, The Netherlands;Laboratory for Pathology East Netherlands, 7555 BB Hengelo, The Netherlands;Ontario Institute for Cancer Research, Toronto, ON M5G OA3, Canada;Pathology DNA, 5223 GZ ’s-Hertogenbosch, The Netherlands;Pathology Laboratory, 3318 AL Dordrecht, The Netherlands;Reinier Haga Medical Diagnostic Center, 2625 AD Delft, The Netherlands;Section of Breast Pathology, Northwestern University, Chicago, IL 60611, USA;Translational Medicine, Bristol-Myers Squibb, Princeton, NJ 08540, USA;

关键词: PD-L1;    SP142;    triple-negative breast cancer;    TNBC;    tumor-infiltrating lymphocytes;    TILs;   

DOI  :  10.3390/cancers13194910

来源: DOAJ

【 摘 要 】

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 vs. 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.

【 授权许可】

Unknown