Spatial heterogeneity of PD-L1 expression and the risk for misclassification of PD-L1 immunohistochemistry in non-small cell lung cancer.
Lung Cancer
; 147: 91-98, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32683207
ABSTRACT
BACKGROUND:
Intra-tumor heterogeneity for PD-L1 expression in non-small cell lung cancer (NSCLC) might lead to inaccurate stratification of patients to immunotherapy. The purpose of this research was to quantitate the effect of different factors on the risk of inaccurate diagnosis of PD-L1 expression.METHODS:
MATLAB software was used to model tumor with a different fraction, distribution and clustering of PD-L1 protein expression and their effect on false positive and negative diagnosis in subsets of the modeled tumor (representing biopsies). Additionally, we evaluated the agreement between PD-L1 status in random segments and whole slides of PD-L1 stained clinical NSCLC cases.RESULTS:
Our computer-based model showed a significant increase in error rate when the fraction of PD-L1 positive cells was closer to the cut-off value (error rate of 33.33 %, 0.45 % and 0.74 % for PD-L1 positivity in 40-60%, ≤20 % and ≥80 % of tumor cells, respectively, Pâ¯<â¯0.0001). In addition, biopsy size showed negative correlation with error rate (Pâ¯<â¯0.0001) and larger clusters of PD-L1 positive cells were associated with higher error rate (Pâ¯<â¯0.0001). Analysis of the clinical samples supported those of the computer-based model with higher error rate in cases with positive PD-L1 expression closer to the cutoff value. Based on our computerized model and clinical analysis, we developed a model to predict error rate based on biopsy size and the fraction of PD-L1 positive cells in the biopsy.CONCLUSION:
Analysis of small biopsies for PD-L1 expression might be associated with significant error rate. The model presented can be used to identify cases with increased risk for error in whom interpretation of the test results should be made with caution.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Israel