Concordance of assessments of four PD-L1 immunohistochemical assays in esophageal squamous cell carcinoma (ESCC)

Given real-world limitations in programmed death-ligand 1 (PD-L1) testing, concordance studies between PD-L1 assays are needed. We undertook comparisons of PD-L1 assays (DAKO22C3, Ventana SP263, Ventana SP142, E1L3N) among observers in esophageal squamous cell carcinoma (ESCC) to provide information on the analytical and clinical comparability of four PD-L1 IHC assays.

Paraffin embedded samples of 50 cases of esophageal squamous cell carcinoma were obtained, satined with all four PD-L1 assays. PD-L1 was evaluated by 68 pathologists from 19 different hospitals. PD-L1 expression was assessed for combined positive score (CPS).

The expression sensitivity of SP263 was the highest in ESCC, followed by 22C3, E1L3N and SP142. Taking CPS 10 as the critical value, inter-observer concordance for CPS scores among 68 physicians was assessed for the 22C3, SP263, SP142, and E1L3N assays, yielding values of 0.777, 0.790, 0.758, and 0.782, respectively. In the comparison between assays, the overall CPS scores concordance rates between 22C3 and SP263, SP142, and E1L3N were 0.896, 0.833, and 0.853, respectively. 22C3 and SP263 have high concordance, with OPA of 0.896, while E1L3N and SP142 have the highest concordance, with OPA of 0.908.

In ESCC, the concordance of PD-L1 evaluation among observers is good, and the immune cell score is still an important factor affecting the concordance of interpretation among observers. Cases near the specific threshold are still the difficult problem of interpretation. SP263 had the highest CPS score of the four assays. SP263 cannot identify all 22C3 positive cases, but had good concordance with 22C3.E1L3N and SP142 showed high concordance.