Abstract 5623: A comparative study of four PD-L1 immunohistochemical assay in non-small cell lung cancer and evaluation of scoring system
Authors: Kim Hyojin , Kwon Hyun Jung , Park Soo Young , Park Eunhyang , Chung Jin-Haeng 
Published: July 2017

Abstract
Background: Clinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated and first line NSCLC patients. At least five PD-L1 IHC assays with custom reagents and scoring-criteria are evaluated in clinical trials. However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not standardized and the role of PD-L1 expression as a biomarker is still controversial.
Materials and Methods: Retrospectively collected formalin-fixed paraffin-embedded whole-tissue sections (WTS) from 97 NSCLC cases from Seoul National University Bundang Hospital were obtained. We tested the samples divided “training set” and “validation set”: A set of 50 NSCLC WTS (32 adenocarcinoma and 18 squamous cell carcinoma) resected from 2010 to 2011 was designated “training set” and the other set of 47 NSCLC WTS (32 adenocarcinoma, 14 squamous cell carcinoma, and 1 pleomorphic carcinoma) resected from 2015 to 2016 was designated “validation set”. We examined PD-L1 protein expression using four different antibodies (Clone E1L3N, SP142, SP263 and 22C3) using Ventana XT platform with optiview detection kit for E1L3N, SP142 and SP263, and DAKO link 46 platform with pharmDx kit for 22C3 by immunohistochemical analysis. Staining of tumor cells (Tumor proportion score, TPS) and immune cells were evaluated.
Results: PD-L1 protein expression was observed in 18 %, 16%, 11% and 12% of total tumors with E1L3N with Ventana optiview kit (5% cutoff), SP142 with Ventana optiview kit with amplification (1% cutoff), SP263 with Ventana optiview kit (25% cutoff) and 22C3 with DAKO PharmDx kit (50% cufoff), respectively. There was no different positive rate between “training” and “validation” set, which means there was no effect of the age of paraffin block on PD-L1 expression. Regarding staining proportion of tumor cells, 22C3 yields more stained tumor cells (highest TPS) and SP142 consistently labels fewer tumor cells (lowest TPS). Among 38 cases which were positive in one or more assays, 28.9% showed discrepant results for PD-L1 expression between the assays according to each criterion. When the same criterion applied for all assays, discrepant rate is higher (63.1 % with 1% cutoff, 71.0% with 5% cutoff).
Conclusion: Although comparative determination of PD-L1 protein levels in NSCLC reveals inter-assay variability of tumor cell staining, positive rate is similar under each criterion. Therefore, there is a potential for different diagnostic results according to the key clinical cut-offs if assays and algorithms are mismatched and we should be careful when interpret the PD-L1 expression with different assays.
Citation Format: Hyojin Kim, Hyun Jung Kwon, Soo Young Park, Eunhyang Park, Jin-Haeng Chung. A comparative study of four PD-L1 immunohistochemical assay in non-small cell lung cancer and evaluation of scoring system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5623. doi:10.1158/1538-7445.AM2017-5623