Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies.
BACKGROUND
High expression of programmed death ligand-1 (PD-L1) on tumor cells (TC) and/or on tumor-infiltrating immune cells (IC) is associated with a high response rate in patients with advanced nonsmall-cell lung cancer (NSCLC) treated with PD-L1 inhibitors. The use of a PD-L1 immunohistochemical (IHC) test in determining the responsiveness to immunotherapy has raised the question of the reliability and reproducibility of its evaluation in lung biopsies compared with corresponding resected surgical specimens.


METHODS
PD-L1 expression in TC and IC was assessed in 160 patients with operable NSCLC on both whole surgical tissue sections and matched lung biopsies, by using a highly sensitive SP142 IHC assay. The specimens were scored as TC 0-3 and IC 0-3 based on increasing PD-L1 expression.


RESULTS
PD-L1 expression was frequently discordant between surgical resected and matched biopsy specimens (the overall discordance rate = 48%; 95% confidence interval 4.64-13.24) and κ value was equal to 0.218 (poor agreement). In all cases, the biopsy specimens underestimated the PD-L1 status observed on the whole tissue sample. PD-L1-positive IC tumors were more common than PD-L1-positive TC tumors on resected specimens. The discrepancies were mainly related to the lack of a PD-L1-positive IC component in matched biopsies.


CONCLUSIONS
Our results indicate relatively poor association of the PD-L1 expression in TC and IC between lung biopsies and corresponding resected tumors. Although these results need to be further validated in larger cohorts, they indicate that the daily routine evaluation of the PD-L1 expression in diagnostic biopsies can be misleading in defining the sensitivity to treatment with PD-L1 targeted therapy.
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice.
M
M
Ilie
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice.
E
E
Long-Mira
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice.
C
C
Bence
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice.
C
C
Butori
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice.
S
S
Lassalle
IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Department of Pneumology.
L
L
Bouhlel
IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice.
L
L
Fazzalari
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice.
K
K
Zahaf
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice.
S
S
Lalvée
Hospital-Related Biobank BB-0033-00025.
K
K
Washetine
IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Department of Thoracic Surgery, Pasteur Hospital, Nice.
J
J
Mouroux
Department of Thoracic Surgery, Pasteur Hospital, Nice.
N
N
Vénissac
Department of Pneumology.
M
M
Poudenx
Department of Pneumology, Centre Antoine Lacassagne, Nice.
J
J
Otto
Laboratory of Cancer Genetics, Department of Pathology, Rouen University Hospital, Rouen, France.
J C
JC
Sabourin
IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Department of Pneumology.
C H
CH
Marquette
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Hospital-Related Biobank BB-0033-00025.
V
V
Hofman
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Hospital-Related Biobank BB-0033-00025 hofman.p@chu-nice.fr.
P
P
Hofman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
NSCLC; PD-L1; biopsy; immunohistochemistry; immunotherapy; surgical resected specimen