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Original Articles
- Interobserver Reproducibility of PD-L1 Biomarker in Non-small Cell Lung Cancer: A Multi-Institutional Study by 27 Pathologists
- Sunhee Chang, Hyung Kyu Park, Yoon-La Choi, Se Jin Jang
- J Pathol Transl Med. 2019;53(6):347-353. Published online October 28, 2019
- DOI: https://doi.org/10.4132/jptm.2019.09.29
- 6,397 View
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- 32 Web of Science
- 30 Crossref
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Abstract
PDF - 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. -
Citations
Citations to this article as recorded by
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- 2,053 View
- 34 Download
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Abstract
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- Recently developed new classifications (Holland, Van Nuys, modified Lagios) of ductal carcinoma in situ (DCIS) linked to outcome have emphasized the importance of nuclear morphology rather than architecture. We have evaluated these three classifications in ductal carcinomas composed of in situ and invasive carcinomas. The reproducibility of three classifications was assessed (n=49), and the histological grade of the DCIS was compared with the histologic differentiation (modified Bloom & Richardson method) and nuclear grade (modified Black method) of the coexisting invasive ductal carcinoma (n=45). According to Holland classification, the DCIS component was poorly differentiated in 51.0%, intermediately differentiated in 40.8%, and well differentiated in 8.2%. Using the Van Nuys classification, the DCIS component was group 3 (high grade with or without necrosis) in 44.9%, group 2 (non-high grade with necrosis) in 28.6%, and group 1 (non-high grade without necrosis) in 26.5%. According to the modified Lagios classification, the DCIS component was high-grade in 42.8%, intermediate-grade in 32.7%, and low-grade in 24.5%. The histologic grades of the three classifications revealed significant correlations between Holland and Van Nuys classification (p<0.0001) and between Holland and modified Lagios classification (p<0.0001), especially in poorly differentiated/group 3/high-grade DCIS. The reproducibility of classification of the DCIS was 71.4% in the Holland, 61.2% in the Van Nuys, and 55.1% in the modified Lagios classifications. The grade of the DCIS showed significant correlation with the grade of coexisting invasive ductal carcinoma (p<0.0001), especially in poorly differentiated/group 3/high-grade DCIS. In conclusion, DCIS grade, determined by the Holland, Van Nuys or modified Lagios classifications, is closely correlated with the histologic grade of the invasive ductal component in tumors composed of in situ and invasive ductal carcinoma, and may be a useful factor to estimate clinical behavior of DCIS. In our experience the Holland classification is recommended for DCIS classification due to its high reproducibility.
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