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J Histochem Cytochem. 2016 Oct;64(10):587-600. doi: 10.1369/0022155416665338. Epub 2016 Sep 2.

Investigation of PD-L1 Biomarker Testing Methods for PD-1 Axis Inhibition in Non-squamous Non-small Cell Lung Cancer.

Author information

1
Department of Pathology, Abbotsford Regional Hospital and Cancer Centre, British Columbia, Canada (BSS)
2
PhenoPath Laboratories, Seattle, Washington (RF, CJ, AMG)
3
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada (BSS, SEK, SZ, SY);
4
Trev and Joyce Deeley Research Centre BC Cancer ,Agency, Vancouver, British Columbia, Canada(KM, BHN)
5
BC Cancer Agency, Vancouver, British Columbia, CanadaDivision of Medical Oncology ,BC Cancer Agency, Vancouver, British Columbia, Canada(GG, JL, CH),
6
BC Cancer Agency, Vancouver, British Columbia, CanadaCanada's Michael Smith Genome Sciences Centre ,BC Cancer Agency, Vancouver, British Columbia, Canada (MJ, EZ, EP, SJMJ, MAM)
7
Department of Laboratory Medicine and Pathology , BC Cancer Agency, Vancouver, British Columbia, Canada(DNI)

Abstract

Inhibitors of the programmed cell death 1 (PD-1) signaling axis have recently demonstrated efficacy and are rapidly being incorporated into the treatment of non-small cell lung cancers (NSCLCs). Despite clear benefits to certain patients, the association of these responses with a predictive biomarker remains uncertain. Several different biomarkers have been proposed, with differing results and conclusions. This study compares multiple methods of biomarker testing for treatment of NSCLCs with PD1-axis inhibitors. Tissue microarrays of matched primary and metastatic NSCLCs were used to compare four different PD-1 ligand (PD-L1) IHC techniques, as well as RNA ISH. Additional cases with whole genome and transcriptome data were assessed for molecular correlates of PD-L1 overexpression. Eighty cases were included in the IHC study. Multiple IHC methodologies showed a high rate of agreement (Kappa = 0.67). When calibrated to RNA expression, agreement improved significantly (Kappa = 0.90, p=0.0049). PD-L1 status of primary and metastatic tumors was discordant in 17 (22%) cases. This study suggests that different IHC methodologies for PD-L1 assessment provide slightly different results. There is significant discordance between the PD-L1 status of primary tumors and lymph node metastases. RNA ISH may be a useful adjunct to complement PD-L1 IHC testing.

KEYWORDS:

NSCLC; PD-1; PD-L1; biomarker; immunotherapy; lung cancer; non–small cell lung carcinoma

PMID:
27591097
PMCID:
PMC5037503
DOI:
10.1369/0022155416665338
[Indexed for MEDLINE]
Free PMC Article

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