title: Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas.
abstract: Immunohistochemistry of the PD-L1 protein may be predictive for anti-PD-1 and anti-PD-L1 immunotherapy in pulmonary adenocarcinoma and in clinically unselected cohorts of so-called non-small-cell lung cancer. Several PD-L1 immunohistochemistry assays with custom reagents and scoring-criteria are developed in parallel. Biomarker testing and clinical decision making would profit from harmonized PD-L1 diagnostics. To assess interobserver concordance and PD-L1 immunohistochemistry staining patterns, 15 pulmonary carcinoma resection specimens (adenocarcinoma: n=11, squamous-cell carcinoma: n=4) were centrally stained with the assays 28-8, 22C3, SP142, and SP263 according to clinical trial protocols. The slides were evaluated independently by nine pathologists. Proportions of PD-L1-positive carcinoma cells and immune cells were scored according to a 6-step system that integrates the criteria employed by the four PD-L1 immunohistochemistry assays. Proportion scoring of PD-L1-positive carcinoma cells showed moderate interobserver concordance coefficients for the 6-step scoring system (Light's kappa=0.47-0.50). The integrated dichotomous proportion cut-offs (≥1, ≥5, ≥10, ≥50%) showed good concordance coefficients (κ=0.6-0.8). Proportion scoring of PD-L1-positive immune cells yielded low interobserver concordance coefficients both for the 6-step-score (κ<0.2) and the dichotomous cut-offs (κ=0.12-0.25). The assays 28-8 and 22C3 stained similar proportions of carcinoma cells in 12 of 15 cases. SP142 stained fewer carcinoma cells compared to 28-8, 22C3, and SP263 in four cases, whereas SP263 stained more carcinoma cells in nine cases. SP142 and SP263 stained immune cells more intensely. The data indicate that carcinoma cells can be reproducibly scored in PD-L1 immunohistochemistry for pulmonary adenocarcinoma and squamous-cell carcinoma. No differences in interobserver concordance were noticed among the tested assays. The scoring of immune cells yielded low concordance rates and might require specific standardization. The four tested PD-L1 assays did not show comparable staining patterns in all cases. Thus, studies that correlate staining patterns and response to immunotherapy are required to test the significance of the observed differences.
authors.affiliation: University Hospital Cologne, Institute of Pathology, Cologne, Germany.
authors.forename: Andreas H
authors.identifier: 0000-0003-0244-1646
authors.initials: AH
authors.lastname: Scheel
authors.affiliation: Charité - University Hospital Berlin, Institute of Pathology, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.affiliation: Institute for Hematopathology Hamburg, Hamburg, Germany.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.affiliation: Charité - University Hospital Berlin, Institute of Pathology, Berlin, Germany.
authors.forename: Korinna
authors.initials: K
authors.lastname: Jöhrens
authors.affiliation: LMU University Hospital Munich, Institute of Pathology LMU Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: LMU University Hospital Munich, Institute of Pathology LMU Munich, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Reu
authors.affiliation: Institute of Pathology Nordhessen, Kassel, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.affiliation: University Hospital Göttingen, Institute of Pathology, Göttingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.affiliation: University Hospital Heidelberg, Institute of Pathology, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Institute for Hematopathology Hamburg, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Tiemann
authors.affiliation: University Hospital Heidelberg, Institute of Pathology, Heidelberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Technical University Munich (TUM), Institute of Pathology, Munich, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: University Hospital Cologne, Medical Clinic I, Cologne, Germany.
authors.forename: Rieke N
authors.initials: RN
authors.lastname: Fischer
authors.affiliation: University Hospital Cologne, Medical Clinic I, Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
authors.affiliation: University Hospital Cologne, Institute of Pathology, Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
mesh_terms: D000230:Adenocarcinoma; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms; D015588:Observer Variation
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human