J Pathol Transl Med.  2019 Nov;53(6):347-353. 10.4132/jptm.2019.09.29.

Interobserver Reproducibility of PD-L1 Biomarker in Non-small Cell Lung Cancer: A Multi-Institutional Study by 27 Pathologists

• Chang S
• Park HK
• Choi YL
• Jang SJ
• Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists

• KMID: 2465433
• DOI: http://doi.org/10.4132/jptm.2019.09.29

Abstract

BACKGROUND
Assessment of programmed cell death-ligand 1 (PD-L1) immunohistochemical staining is used for treatment decisions in non-small cell lung cancer (NSCLC) regarding use of PD-L1/programmed cell death protein 1 (PD-1) immunotherapy. The reliability of the PD-L1 22C3 pharmDx assay is critical in guiding clinical practice. The Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists investigated the interobserver reproducibility of PD-L1 staining with 22C3 pharmDx in NSCLC samples.
METHODS
Twenty-seven pathologists individually assessed the tumor proportion score (TPS) for 107 NSCLC samples. Each case was divided into three levels based on TPS: <1%, 1%-49%, and ≥50%.
RESULTS
The intraclass correlation coefficient for TPS was 0.902±0.058. Weighted κ coefficient for 3-step assessment was 0.748±0.093. The κ coefficients for 1% and 50% cut-offs were 0.633 and 0.834, respectively. There was a significant association between interobserver reproducibility and experience (formal PD-L1 training, more experience for PD-L1 assessment, and longer practice duration on surgical pathology), histologic subtype, and specimen type.
CONCLUSIONS
Our results indicate that PD-L1 immunohistochemical staining provides a reproducible basis for decisions on anti-PD-1 therapy in NSCLC.

Keyword

Programmed cell death-ligand 1; Reproducibility; Observer variation; Immunohistochemistry

MeSH Terms

Carcinoma, Non-Small-Cell Lung*
Cell Death
Immunohistochemistry
Immunotherapy
Observer Variation
Pathology

Figure

• 

  Fig. 1. Programmed cell death-ligand 1 (PD-L1) immunohistochemistry results in non-small cell lung cancer patients using 22C3 antibody on fully automated Dako Autostainer Link 48 platform. (A) Negative staining for PD-L1. (B) PD-L1 tumor proportion score (TPS) of 10%. (C) PD-L1 TPS of 70%. (D) PD-L1 TPS of 100%.

• 

  Fig. 2. (A) Few tumor cells show weak and partial membrane staining for programmed cell death-ligand 1 (PD-L1) antibody. (B) Tumor associated immune cells show strong staining with lack of PD-L1 staining in tumor cells. (C) Tumor cells show heterogeneous membrane staining pattern with various staining intensities. (D) Tumor shows patchy membrane staining pattern.

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