Spatial heterogeneity of PD-L1 expression and the risk for misclassification of PD-L1 immunohistochemistry in non-small cell lung cancer.

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Shani Ben DoriDov Hershkovitz

Abstract

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. 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. 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, P < 0.0001). In addition, biopsy size showed negative correlation with error rate (P < 0.0001) and larger clusters of PD-L1 positive cells were associated with higher error rate (P < 0.0001). Analysis of the clinical samples supported those of the computer-based model with higher error rate in cases with positive PD-...Continue Reading

Citations

Oct 8, 2020·Pathology International·Eiji MatsumuraOkio Hino
Feb 14, 2021·Nature Reviews. Clinical Oncology·Deborah Blythe DoroshowFred R Hirsch
Feb 26, 2021·Seminars in Cancer Biology·Yin WuCharles Swanton

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