Abstract
Background: Expression of programmed death ligand 1 (PD-L1) is used to predict response to PD-1/PD-L1 inhibitors in multiple types of cancer. Soon, it will be incorporated in clinical practice for patients with head and neck squamous cell carcinoma (HNSCC) as well. However, several antibodies and immunohistochemical staining platforms are available for PD-L1 testing and multiple scoring methods are used. This study aimed to compare the performance of two PD-L1 standardized assays and one laboratory-developed test (LDT) in HNSCC using the tumor proportion score (TPS) and the combined positive score (CPS).
Materials and methods: Pre-treatment biopsies from a cohort of 147 head and neck cancer patients were included in a tissue-microarray. The cohort consisted of stage III and IV, HPV negative oropharyngeal, hypopharyngeal and laryngeal cancer patients that qualified for chemoradiotherapy with a curative intent. Serial sections of the TMA were immunohistochemically stained for PD-L1 expression using SP263 on the Ventana Benchmark Ultra platform (Ventana Medical Systems, Tucson, AZ), 22C3 on the Dako Link 48 platform (Dako, Carpinteria, Ca), and 22C3 as an LDT on the Ventana Benchmark Ultra. The stained slides were assessed by two researchers; discrepancies were resolved by consensus. Stainings were assessed for TPS and CPS. The TPS was defined as the number of positive tumor cells divided by the total number of viable tumor cells multiplied by 100%; the CPS as the number of positive tumor cells, lymphocytes and macrophages, divided by the total number of viable tumor cells multiplied by 100%. Clinically relevant cut-offs of ≥1% and ≥50% for TPS and ≥1% and ≥20% for CPS were used. Concordance was analyzed using the intraclass correlation coefficient (ICC) and weighted kappa analysis.
Results: PD-L1 positivity in our HNSCC patient cohort was low when using cut-offs of 50% for TPS and 20% for CPS (table). Overall, concordance between the different staining assays was moderate for TPS (ICC 0.70) as well as for CPS (ICC 0.53). When stratifying patients by clinically relevant cut-offs, considerable differences between the assays were observed: for TPS, concordance was still moderate (kappa 0.56), while for CPS, concordance was poor (kappa 0.44). Generally, SP263 stained a higher percentage of cells than the other two assays. Especially when including immune cells in the scoring method by using the CPS, the SP263 antibody showed a higher PD-L1 positivity rate.
Conclusions: Moderate concordance was shown between three PD-L1 immunohistochemical staining assays and considerable differences in PD-L1 positivity were observed when using clinically relevant cut-offs. This should be taken into account when using PD-L1 expression cut-offs to guide clinical practice.
Materials and methods: Pre-treatment biopsies from a cohort of 147 head and neck cancer patients were included in a tissue-microarray. The cohort consisted of stage III and IV, HPV negative oropharyngeal, hypopharyngeal and laryngeal cancer patients that qualified for chemoradiotherapy with a curative intent. Serial sections of the TMA were immunohistochemically stained for PD-L1 expression using SP263 on the Ventana Benchmark Ultra platform (Ventana Medical Systems, Tucson, AZ), 22C3 on the Dako Link 48 platform (Dako, Carpinteria, Ca), and 22C3 as an LDT on the Ventana Benchmark Ultra. The stained slides were assessed by two researchers; discrepancies were resolved by consensus. Stainings were assessed for TPS and CPS. The TPS was defined as the number of positive tumor cells divided by the total number of viable tumor cells multiplied by 100%; the CPS as the number of positive tumor cells, lymphocytes and macrophages, divided by the total number of viable tumor cells multiplied by 100%. Clinically relevant cut-offs of ≥1% and ≥50% for TPS and ≥1% and ≥20% for CPS were used. Concordance was analyzed using the intraclass correlation coefficient (ICC) and weighted kappa analysis.
Results: PD-L1 positivity in our HNSCC patient cohort was low when using cut-offs of 50% for TPS and 20% for CPS (table). Overall, concordance between the different staining assays was moderate for TPS (ICC 0.70) as well as for CPS (ICC 0.53). When stratifying patients by clinically relevant cut-offs, considerable differences between the assays were observed: for TPS, concordance was still moderate (kappa 0.56), while for CPS, concordance was poor (kappa 0.44). Generally, SP263 stained a higher percentage of cells than the other two assays. Especially when including immune cells in the scoring method by using the CPS, the SP263 antibody showed a higher PD-L1 positivity rate.
Conclusions: Moderate concordance was shown between three PD-L1 immunohistochemical staining assays and considerable differences in PD-L1 positivity were observed when using clinically relevant cut-offs. This should be taken into account when using PD-L1 expression cut-offs to guide clinical practice.
| Original language | English |
|---|---|
| Pages (from-to) | S20-S20 |
| Number of pages | 1 |
| Journal | European Journal of Cancer |
| Volume | 110 |
| Issue number | supplement 1 |
| DOIs | |
| Publication status | Published - Mar 2019 |