PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project

Abstract

BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

“…However, several studies, including our own, have previously shown that the PD‐L1 IHC results from whole sections and small materials (e.g. biopsy or TMA) are largely comparable . Therefore, TMA can serve as an affordable alternative in evaluating inter‐ and intraobserver agreement for PD‐L1 IHC in the research setting.…”

“…Similarly, the ICC is lower for SP142 clone compared with the other three clones when evaluating raw positive TC or IC percentages, being 0.689–0.694 compared with 0.834–0.983 of ICC from the other three antibody clones. SP142 clone has been previously shown to preferentially stain IC with a significantly lower percentage of TC staining in NSCLC, UC and HSCC . As the evaluators have remained the same for all antibody clones, it is likely that the unique staining properties of the SP142 clone is the cause of variable PD‐L1 readout.…”

“…To date, only a limited number of publications have studied the consistency and accuracy of PD‐L1 evaluation by investigating the interobserver agreement on PD‐L1 scoring among pathologists. Most studies focused exclusively on NSCLC, while only two studies included HSCC, one included UC and none included for BC . Table provides a literature review of these studies.…”

“…The reported κ ranges from 0.58 to 0.96. Two studies have reported a poor interobserver agreement when evaluating IC in NSCLC with a κ‐value of <0.3 . It is postulated that the poor interobserver concordance among pathologists in scoring IC in NSCLC may be secondary to a lack of experiences in evaluating IC, as most of the PD‐L1 clinical algorithms in NSCLC do not include routine evaluation of IC .…”

Programmed death ligand 1 immunohistochemistry: can we agree on this?

“…In this issue of Histopathology , authors Downes and colleagues interrogate the reproducibility of PD‐L1 interpretation utilising four different assays, including the pembrolizumab companion diagnostic assay 22C3 (pharmDx), the atezolizumab assay utilising SP142 (Ventana/Roche, Tucson, AZ, USA), the durvalumab complementary diagnostic SP263 and a laboratory‐developed test utilising the E1L3N clone . Inter‐ and intra‐observer reproducibility and inter‐assay reproducibility for PD‐L1 immunohistochemistry has been studied extensively in NSCLC, but few studies have examined the performance of these tests in tumours outside the lung. Applying staining thresholds defined by clinical trials, as well as raw tumour and immune cell percentage positivity, the authors demonstrate substantial concordance between pathologists reviewing PD‐L1 staining of urothelial, breast and head and neck squamous carcinomas using the SP263, 22C3 and E1L3N tests.…”