Comparison of assessment of programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer biopsies and surgical specimens

Abstract

AimsProgrammed death-ligand 1 (PD-L1) status in triple-negative breast cancer (TNBC) is important for immune checkpoint inhibitor therapies but may vary between different immunohistochemical assays, scorings and the type of specimen used for analysis.MethodsWe compared the analytical concordance of three clinically relevant PD-L1 assays (VENTANA SP142, VENTANA SP263 and DAKO 22C3 pharmDx) assessing immune cell score (IC), tumour proportion score and combined positive score (CPS) in preoperative biopsies and resection specimens of primary TNBC. PD-L1 expression was scored on virtual whole slide images and compared with expression data from corresponding surgical specimens.ResultsThe mean PD-L1 positivity in TNBC biopsies defined as IC ≥1% and CPS ≥1 ranged between 11% and 61% with the lowest positivity for SP142 and highest for SP263. The corresponding surgical specimens showed overall higher positivity rates (53%–75%). When comparing biopsies with surgical specimens, the agreement for PD-L1 positivity with SP263 and 22C3 at IC score ≥1% and CPS ≥1 was fair (kappa 0.47–0.52) and poor for SP142 (kappa 0.15–0.19). Using CPS ≥10 cut-off, the agreement for SP263 was excellent (kappa 0.751) but poor for 22C3 (kappa 0.261). Spearman correlation coefficients ranged between 0.489 and 0.75 indicating a generally moderate to strong correlation between biopsies and surgical specimens for all assays and scores.ConclusionsWe demonstrate high accordance between biopsies and surgical specimens for SP263 and 22C3 scoring but less for SP142. Generally, biopsies are suitable for PD-L1 testing in TNBC but the appropriate assay, scoring and cut-off must be considered.

Diagnostic biopsy does not accurately reflect the PD-L1 expression in triple-negative breast cancer

“…Samples in which the estimated PD-L1 expression was near the cutoff also had a higher risk of error. Surprisingly, the false positives in their study were higher than the false negatives, showing a trend contradictory to other literature reports [ 12 – 14 ].…”

“…Only a few studies have addressed the role of PD-L1 heterogeneity in tumor misclassification. Noske et al examined PD-L1 expression in TNBC using VENTANA SP142, VENTANA SP263, and DAKO 22C3 assays [ 12 ]. PD-L1 positivity was defined as > 1% of the percentage of tumor area covered by tumor-infiltrating immune cells (IC) and when the percentage of all stained cells in relation to all viable cells in a sample was > 1%.…”

“…The concordance rates between biopsies and resection specimens were 78% for SP263, 72% for 22C3, and 54% for SP142. No significant correlation existed between the PD-L1 status of biopsies and surgical specimens assessed by the SP142 test [ 12 ]. Hence, SP142 may not be the most suitable to assess PD-L1 expression in TNBC.…”

Tumor Infiltrating Lymphocytes (TILS) and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications from Pathologist’s Perspective

“…Based on the results of the IMpassion130 trial, the Ventana PD-L1 SP142 test (IC score ≥ 1%) has been approved by the FDA for the selection of advanced TNBC or mTNBC suitable for combination therapy with Atezolizumab plus nab-paclitaxel [ 42 ]. Based on the same cohort, a post hoc harmonization study attempted to evaluate the inter-assay variability of three PD-L1 assays, namely the Ventana SP142 and SP263 and the Dako 22C3 [ 59 ]. IC score (≥1%) was utilized for SP142 and SP263 assays, while CPS score (≥1) was evaluated for the 22C3 assay [ 59 ].…”

“…Based on the same cohort, a post hoc harmonization study attempted to evaluate the inter-assay variability of three PD-L1 assays, namely the Ventana SP142 and SP263 and the Dako 22C3 [ 59 ]. IC score (≥1%) was utilized for SP142 and SP263 assays, while CPS score (≥1) was evaluated for the 22C3 assay [ 59 ]. Interestingly, 22C3 and SP263 clones individuated a higher rate of PD-L1 positive patients (81% and 75%, respectively) compared with the SP142 clone (46%) [ 59 ].…”