PD-L1 immunohistochemical assays for assessment of therapeutic strategies involving immune checkpoint inhibitors in non-small cell lung cancer: a comparative study

Abstract

// Hyojin Kim 1 , Hyun Jung Kwon 1 , Soo Young Park 1 , Eunhyang Park 1 and Jin-Haeng Chung 1, 2 1 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 2 Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea Correspondence to: Jin-Haeng Chung, email: chungjh@snu.ac.kr Keywords: programmed cell death-ligand 1; immunotherapy; immunohistochemistry; biopsy; non-small cell lung cancer Received: May 04, 2017      Accepted: August 28, 2017      Published: October 06, 2017 ABSTRACT Although immune checkpoints inhibitors have exhibited promising activity in clinical trials in non-small cell lung cancer (NSCLC) patients, the current programmed cell death-ligand 1 (PD-L1) assays are inconsistent in terms of the staining analysis and scoring system used. To verify the interchangeability of the available PD-L1 assays, we performed immunohistochemistry using three antibody clones used in clinical trials (22C3, SP263, and SP142) and the E1L3N clone as a laboratory developed test for 97 resected NSCLC specimens. Matched tissue microarray specimens were also stained. Staining with 22C3 yielded a greater proportion of stained tumor cells, whereas SP142 staining consistently labelled fewer tumor cells. However, when various cut-off criteria were applied, the positivity rates for PD-L1 were similar, with high concordance, under assay-specific cut-offs. Moreover, seven cases of discordant PD-L1 expression between the resected specimen and matched tissue microarray specimens were observed. In conclusion, despite of inter-assay variability of the PD-L1 status in NSCLC, the positivity rate appears to be similar under assay-specific criteria. Hence, an appropriate clinically defined algorithm or cut-off should be separately applied for each assay. Moreover, multiple biopsy specimens from different tumor areas should be obtained to reduce false results due to intratumoral heterogeneity in PD-L1 expression.