13P Comparison study of different programmed death-ligand 1 (PD-L1) assays, readers and scoring methods in triple-negative breast cancer (TNBC)

Important role of Nfkb2 in the KrasG12D-driven carcinogenesis in the pancreas

Abstract Background Oncogenic Kras initiates and drives carcinogenesis in the pancreas by complex signaling networks, including activation of the NFκB pathway. Although recent evidence has shown that oncogenic gains in Nfκb2 collaborate with Kras in the carcinogenesis, no data at the level of genetics for the contribution of Nfκb2 is available so far. Methods We used Nfkb2 knock-out mice to decipher the role of the gene in Kras-driven carcinogenesis in vivo. Results We show that the Nfkb2 gene is needed for cancer initiation and progression in KrasG12D-driven models and this requirement of Nfkb2 is mechanistically connected to proliferative pathways. In contrast, Nfκb2 is dispensable in agg…

Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple-negative breast cancer (TNBC)

Abstract Background Atezolizumab (an anti–PD-L1 antibody) has shown clinical activity alone or in combination with nab-paclitaxel in patients (pts) with first-line metastatic TNBC who have PD-L1 expression on their tumour-infiltrating immune cells (IC). We analysed the performance of 4 PD-L1 IHC assays for PD-L1 IC expression in TNBC. Methods Thirty archival TNBC tissue specimens were selected from a set of 107 based on PD-L1 IC expression per VENTANA SP142 ( 5%: 8 cases), to represent the distribution of PD-L1 IC–positivity in the pivotal atezolizumab studies (Emens et al., SABCS 2018; JAMA Oncol 2019). Serial histologic sections were stained with VENTANA SP142 and SP263, and DAKO 22C3 and…

A multicentre analytical comparison study of inter-reader and inter-assay agreement of four programmed death-ligand 1 immunohistochemistry assays for scoring in triple-negative breast cancer.

AIMS Studies in various cancer types have demonstrated discordance between results from different programmed death-ligand 1 (PD-L1) assays. Here, we compare the reproducibility and analytical concordance of four clinically developed assays for assessing PD-L1-positivity in tumour-infiltrating immune cells in the tumour area (PD-L1-IC-positivity) in triple-negative breast cancer (TNBC). METHODS AND RESULTS Primary TNBC resection specimens (n = 30) were selected based on their PD-L1-IC-positivity per VENTANA SP142 ( 5%: eight cases). Serial histological sections were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3 and DAKO 28-8. PD-L1-IC-positivity and tumour cell expression (…

Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple negative breast cancer (TNBC)

Abstract Background Atezolizumab (an anti–PD-L1 antibody) has shown clinical activity alone or in combination with nab-paclitaxel in patients (pts) with first-line metastatic TNBC who have PD-L1 expression on their tumour-infiltrating immune cells (IC). We analysed the performance of 4 PD-L1 IHC assays for PD-L1 IC expression in TNBC. Methods Thirty archival TNBC tissue specimens were selected from a set of 107 based on PD-L1 IC expression per VENTANA SP142 ( 5%: 8 cases), to represent the distribution of PD-L1 IC–positivity in the pivotal atezolizumab studies (Emens et al., SABCS 2018; JAMA Oncol 2019). Serial histologic sections were stained with VENTANA SP142 and SP263, and DAKO 22C3 and…

Interassay and interobserver comparability study of four programmed death-ligand 1 (PD-L1) immunohistochemistry assays in triple-negative breast cancer

Different immunohistochemical programmed death-ligand 1 (PD-L1) assays and scorings have been reported to yield variable results in triple-negative breast cancer (TNBC). We compared the analytical concordance and reproducibility of four clinically relevant PD-L1 assays assessing immune cell (IC) score, tumor proportion score (TPS), and combined positive score (CPS) in TNBC. Primary TNBC resection specimens (n = 104) were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28–8. PD-L1 expression was scored according to guidelines on virtual whole slide images by four trained readers. The mean PD-L1 positivity at IC-score ≥1% and CPS ≥1 ranged between 53% and 75% with th…